First real-world experience with 1L pembrolizumab and chemotherapy treatment for advanced triple-negative breast cancer in Poland: safety analysis and first survival outcomes from a multicenter cohort

First real-world experience with 1L pembrolizumab and chemotherapy treatment for advanced triple-negative breast cancer in Poland: safety analysis and first survival outcomes from a multicenter cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article First real-world experience with 1L pembrolizumab and chemotherapy treatment for advanced triple-negative breast cancer in Poland: safety analysis and first survival outcomes from a multicenter cohort Małgorzata Pieniążek, Aleksandra Konieczna, Katarzyna Świderska, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7367639/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Pembrolizumab combined with chemotherapy has improved clinical outcomes in PD-L1-positive metastatic triple-negative breast cancer (mTNBC) in KEYNOTE-355 trial. However, real-world studies confirming these data are lacking. We aimed to evaluate the efficacy and safety of pembrolizumab with chemotherapy in a real-world cohort of Polish patients with PD-L1-positive (CPS ≥ 10), previously untreated mTNBC. Methods This retrospective study included 89 female patients, who initiated this regimen between September 2022 and February 2025 at thirteen Polish oncology centers. Patients received pembrolizumab combined with paclitaxel or carboplatin/gemcitabine as per Polish reimbursement criteria. Primary endpoints included overall survival (OS), progression-free survival (PFS), and safety, assessing immune-related adverse events (irAEs) and chemotherapy-related toxicities (trAEs) according to CTCAE v5.0 criteria. Results The median follow-up was 10.1 months (IQR 5.5–14.8). OS data were immature (n = 15 events). Median PFS was 9.3 months (95% CI: 6.6–14.7). A higher number of metastatic sites was significantly associated with shorter PFS (HR = 1.43, 95% CI: 1.09–1.88, p = 0.01), while other clinical and treatment parameters showed no significant associations. irAEs occurred in 37.1% (n = 33) of patients, one-third were grade 3/4. Neither irAE occurrence (p = 0.55) nor corticosteroid use (p = 0.67) significantly impacted PFS. Conclusion In this real-world cohort of first-line pembrolizumab plus chemotherapy for PD-L1-positive mTNBC, treatment achieved meaningful efficacy and an acceptable safety profile, with median PFS broadly consistent with clinical trial results. OS data remain immature. Clinical parameters showed limited prognostic value, suggesting a need for integrating molecular biomarkers and tumor biology into treatment selection and prognostication to optimize patient outcomes. pembrolizumab metastatic triple negative breast cancer real world data first line treatment progression-free survival safety Figures Figure 1 Figure 2 Introduction Immunotherapy using anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies, alone or in combination with chemotherapy, has significantly improved outcomes in many advanced solid tumors [ 1 – 3 ]. Although historically breast cancer has been considered immunologically "cold," triple-negative breast cancer (TNBC) - a distinct molecular subtype - has emerged as a promising candidate for immune-based therapeutic approaches [ 4 – 6 ]. This potential arises primarily from its higher levels of tumor-infiltrating lymphocytes (TILs), increased PD-L1 expression, and elevated tumor mutational burden (TMB) compared to other breast cancer subtypes [ 5 , 6 ]. Advances in genomic profiling have also identified immune-enriched basal-like tumors that may be particularly responsive to immunotherapy [ 7 , 8 ]. The aggressive course of metastatic TNBC (mTNBC) and the limited survival benefit of standard chemotherapy underscore the need for improved treatments [ 9 , 10 ]. Phase III trials have shown that adding immunotherapy to chemotherapy can provide clinical benefit, particularly in PD-L1-positive disease. In IMpassion130, atezolizumab plus nab-paclitaxel significantly improved progression-free survival (PFS) in PD-L1-positive patients, with a clinically meaningful but not statistically significant overall survival (OS) gain [ 11 , 12 ]. In contrast, IMpassion131, using standard paclitaxel, showed no PFS improvement [ 13 ]. Further evidence from KEYNOTE-355 demonstrated that pembrolizumab plus chemotherapy significantly improved both PFS and OS in patients with PD-L1–positive mTNBC (Combined Positive Score [CPS] ≥ 10) [ 14 , 15 ], establishing it as a standard first-line treatment option [ 16 , 17 ]. Meta-analyses confirm that chemoimmunotherapy improves PFS and shows a trend toward OS benefit in PD-L1–positive mTNBC, with limited effect in PD-L1–negative disease [ 18 – 21 ]. Pembrolizumab plus chemotherapy appears to have broader efficacy in the intention-to-treat population, whereas atezolizumab benefits are largely confined to PD-L1–positive patients [ 22 , 23 ]. Despite strong trial evidence, real-world data (RWD) for pembrolizumab in this setting are lacking. Available RWD suggest that first-line immune checkpoint inhibitor (ICI) use yields better outcomes than later lines, emphasizing the importance of treatment timing [ 24 , 25 ] In Poland, pembrolizumab has been reimbursed within the Ministry of Health drug program since July 2023 [ 26 ], making evaluation of its real-world effectiveness and safety highly relevant. The primary aim of this study was to assess PFS and OS, and describe adverse events (AEs), in patients treated with pembrolizumab plus chemotherapy. We also sought to identify factors associated with outcomes, including time from radical treatment to metastatic relapse, time from relapse to systemic therapy initiation, and baseline clinical characteristics. Materials and Methods Study population and treatment Between September 2022 and February 2025, pembrolizumab combined with chemotherapy was initiated in 89 female patients diagnosed with advanced TNBC across thirteen oncology centers in Poland (listed in Table S1 - Supplementary Appendix). Patients were identified via hospital databases and the Polish National Health Fund registry system. Inclusion criteria followed the Polish drug reimbursement guidelines based on the KEYNOTE-355 trial protocol [ 26 , 27 ], requiring histologically confirmed TNBC according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) standards, confirmed PD-L1 positivity (CPS ≥ 10) assessed by a validated assay, and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 [ 28 ]. Additionally, patients had to exhibit inoperable or metastatic disease, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, sufficient organ function, no active metastases in the central nervous system, and no previous systemic treatment for advanced disease or at least six months relapsed since completion of prior curative-intent therapy. Treatment was discontinued at the time of progressive disease, unacceptable toxicity, deterioration of performance status or quality of life, or upon decision by the patient or treating physician. A comprehensive description of inclusion and exclusion criteria aligned with Polish reimbursement regulations is provided in the Supplementary Appendix. Patients receiving pembrolizumab under a different funding method (outside clinical trials) were also eligible for inclusion. Pembrolizumab was administered intravenously at doses of either 200 mg every three weeks or 400 mg every six weeks, according to physician preference. The chemotherapy regimen was selected individually by the treating oncologist, consistent with recommendations outlined in the European Union Summary of Product Characteristics (SmPC), including paclitaxel administered intravenously at 90 mg/m² body surface area on days 1, 8, and 15 every 28 days, or gemcitabine at 1000 mg/m² body surface area combined with carboplatin (AUC 2 mg/mL/min) on days 1 and 8 every 21 days [ 29 ]. AEs were monitored and graded following the National Cancer Institute’s Common Terminology Criteria for AEs (NCI-CTCAE), version 5.0 [ 30 ]. Modifications to treatment doses following AEs were implemented based on recommendations from the SmPC [ 29 ]. Treatment efficacy was evaluated every three months by chest, abdomen or pelvis imaging (mostly using computed tomography (CT) or in special clinical situations magnetic resonance imaging (MRI)) according to RECIST, version 1.1 [ 28 ]. Data collection Data were collected retrospectively using information extracted from both electronic and paper medical records with cut-off on August 5, 2025. To ensure clarity and completeness, the dataset was organized into multiple categories. Demographic data included patient age at the time of diagnosis and at initiation of palliative systemic therapy. Pathological parameters comprised human epidermal growth factor receptor 2 (HER2) expression, histological grade, and the Ki-67 proliferation index, assessed using either the initial diagnostic material or the most recent biopsy available. Clinical characteristics included the date of diagnosis of mTNBC, the extent of disease dissemination (defined by the number of metastatic sites, count of measurable lesions, and size of the largest lesion) and patient-related factors such as ECOG PS and body mass index (BMI) at therapy onset. Information regarding the type and intent of initial treatment (curative or palliative), the date of completion of systemic radical approach, and the time point of disease progression to metastatic stage was also collected. Treatment-related variables focused on pembrolizumab-based therapy, including the start date, type of chemotherapy (paclitaxel or carboplatin with gemcitabine), and date of the last administered dose. Details regarding chemotherapy dose adjustments and any concurrent radiotherapy were also captured. AEs associated with both immunotherapy and chemotherapy were documented according to severity using the NCI-CTCAE version 5.0 criteria, along with the use of corticosteroids when clinically indicated for AE management. The dataset further included details on subsequent lines of therapy following pembrolizumab-based treatment, information on the timing of the last clinical assessment and, if applicable, the date of death. Primary and secondary objectives The primary objective of this study was to evaluate PFS, OS, and to characterize AEs in a real-world Polish cohort of women diagnosed with mTNBC and PD-L1 expression (CPS ≥ 10), treated with pembrolizumab in combination with chemotherapy. OS was defined as the time from initiation of pembrolizumab-based treatment to death from any cause, while PFS was defined as the time from treatment initiation to documented disease progression or death, whichever occurs first. The secondary objectives focus on identifying clinical, patient-, disease-, and treatment-related factors that may be associated with PFS and OS. Specifically, the study investigates whether the duration between completion of radical treatment and the onset of metastatic disease, as well as the time from diagnosis of metastatic relapse to initiation of systemic therapy, correlate with survival outcomes. Patient-related characteristics such as age at treatment initiation, baseline ECOG PS, and BMI are also analyzed for potential associations with PFS and OS. Additionally, disease-related features including the number of metastatic sites, the number of measurable lesions, the size of the largest lesion, and overall measurable tumor burden are examined for their prognostic value. Treatment-related factors were explored as well, including the type of chemotherapy regimen administered (paclitaxel, carboplatin, or carboplatin combined with gemcitabine), any reductions in chemotherapy dose, and the use of radiotherapy during treatment. Finally, the study evaluated the impact of immune-related AEs (irAEs) on clinical outcomes, specifically assessing whether the occurrence and severity of irAEs influence PFS and OS, and whether the use of corticosteroids for irAE management affects treatment efficacy. Treatment-related AE (trAEs) and irAEs were assessed as in the clinical trial setting, that is, based on the treating physician’s individual judgment. The Ethics Committee of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw Branch, Poland, reviewed and approved this retrospective analysis (approval no. 51/2025, issued on May 29, 2025). Statistical analysis Continuous variables were summarized using medians and interquartile ranges (IQR, 1st–3rd quartiles), as their distributions for both PFS and OS significantly deviated from normality (Shapiro-Wilk test). Categorical variables were described using frequencies and percentages. The selection of variables for correlation and regression analyses was based on clinical relevance, expert opinion, and previously published evidence. The association between explanatory variables and PFS or OS was assessed using multivariate Cox proportional hazards regression models. Variables for inclusion were primarily selected according to prior research findings. For PFS, separate initial Cox models were built for three domains: (1) clinical characteristics, (2) disease burden, and (3) treatment-related factors. In the disease burden model (n = 79, events = 45), the initial set of variables comprised number of metastatic lesion locations, number of measurable lesions, tumor burden, and size of the largest lesion. Due to violations of the proportional hazards assumption, number of measurable lesions and tumor burden were removed. The final adjusted model retained number of metastatic lesion locations and size of the largest lesion. In the treatment-related model (n = 87, events = 48), the initial variables were radiotherapy, chemotherapy dose reduction and chemotherapy regimen. Chemotherapy dose reduction violated the proportional hazards assumption and was excluded. Kaplan–Meier analyses demonstrated crossing survival curves for both OS and PFS; therefore, the Peto–Peto log-rank test, which does not assume proportional hazards, was applied for group comparisons. All statistical analyses were performed using R (version 4.4.0) and Python (version 3.11.4), with statistical significance set at α = 0.05. Results Baseline patient characteristics Clinical data were collected from 89 women treated with pembrolizumab-based therapy. The median age at initial diagnosis was 54 years (IQR: 45–63), increasing to 58 years (IQR: 48–67) at the start of systemic treatment. The majority of patients were postmenopausal and had at least one comorbid condition. A BReast CAncer gene ( BRCA ) mutation was identified in approximately one-sixth of the cohort, while about one-quarter had not undergone genetic testing. PD-L1 expression, assessed by CPS, varied between centers. For 17 patients, the result was reported qualitatively as “>10”, whereas in the remaining cases (n = 72) quantitative values were available, with a median CPS of 20 (IQR: 15–50). Invasive ductal carcinoma was the predominant histological subtype. Tumors exhibited aggressive features: most were classified as histological grade 3, and the median Ki-67 proliferation index was 70% (IQR: 40–80). Metastatic spread most commonly involved the lymph nodes and lungs. The median number of metastatic sites was 2 (IQR: 1–3). The total sum of the largest dimensions of all measurable lesions in a CT scan performed prior to the initiation of the treatment had a median of 81.0 mm (IQR: 50.0–132.8). The number of measurable lesions varied. A comprehensive summary of patient and disease characteristics is provided in Table 1 . Table 1 Characteristic of patients and the disease Category Parameter Number and Percentage (N = 89 (100%)) Patient Characteristics Menopausal status Premenopausal n(%) 16(18) Perimenopausal n(%) 11(12.4) Postmenopausal n(%) 61(68.5) Unknown n(%) 1(1.1) Comorbidities No 36(40.4) Yes 53(59,6) BRCA mutation Not present n(%) 55(61.8) Present n(%) 16(18) Not tested n(%) 18(20.2) Disease Characteristics Histological grade Grade 3 n(%) 53(59.6) Grade 2 n(%) 29(32.6) Grade 1 n(%) 2(2.2) Lack of data n(%) 5(5.6) Histological subtype Invasive ductal n(%) 78(87.6) Metaplastic n(%) 6(6.7) Invasive lobular n(%) 3(3.4) Others n(%) 2(2.3) HER-2 IHC 0 n(%) 52(58.4) 1 n(%) 28(31.5) 2 * n(%) 9 (10.1) Site of metastatic disease Lymph nodes n(%) 56 (62.9) Lung n(%) 43 (48.3) Bones n(%) 28 (31.5) Liver n(%) 20 (22.5) Skin/subcutaneous tissue n(%) 15 (16.9) Malignant effusion n(%) 12 (13.5) Brain n(%) 9 (10.1) Other n(%) 12 (13,5%) Number of measurable lesions 1–3 n(%) 35 (39.3) 4–10 n(%) 29 (32.6) 10–20 n(%) 9 (10.1) >20 n(%) 6 (6.7) Only non-measurable lesions n(%) 8 (9) Unknown n(%) 2 (2,3%) Abbreviation : BRCA, BReast CAncer gene; HER2, human epidermal growth factor receptor 2, IHC, immunohistochemistry * Negative in situ hybridization (ISH) result Treatment exposure and outcomes The median follow-up was 10.1 months (IQR 5.5–14.8). Most patients (62, 69.7%) received carboplatin combined with gemcitabine, while 26 (29.2%) were treated with paclitaxel. One patient received carboplatin monotherapy based on physician discretion. All patients were administered pembrolizumab at a dose of 200 mg intravenously every three weeks. Among those who completed treatment, the median number of pembrolizumab doses was 6 (IQR 5–9) and the median treatment time was 5.5 months (IQR 3.7–9.9). The best treatment response was partial response (PR) in 39 (43.8%) patients and complete response (CR) in 3 ((3.4%). Stable disease (SD) was observed in 34 (38.2%) patients. Response data were unavailable for 6 (6.7%) individuals. Notably, only 7 (7.9%) patients showed tumor progression at the first radiological assessment. Survival outcomes OS data were immature due to the low number of events (n = 15; 16.9%). Preliminary observations suggest a possible trend toward longer OS in patients treated with curative intent in the past compared with patients diagnosed with de novo metastatic BC. For those, who died, OS ranged from 0.2 to 26.2 months (Fig. 1 ). Median PFS (mPFS) was 9.3 months (95% CI: 6.6–14.7). Subgroup analysis showed that patients with prior curative treatment (n = 58; 65.2%) had mPFS of 7.2 months (95% CI: 5.8–14.7), whereas data for patients with de novo metastatic disease (n = 31; 34.8%) remained immature (Fig. 2 ). Prognostic impact of time intervals on PFS The median interval between the end of radical treatment and the diagnosis of metastatic disease was 21.3 months (95% CI: 13.7–27.2). The median interval from metastatic diagnosis to treatment initiation was 1.58 months (95% CI: 1.31–1.94) In the multivariate analysis of PFS, neither the interval from the end of radical treatment to metastatic diagnosis (HR = 1.00, p = 0.36) nor the interval from metastatic diagnosis to treatment initiation (HR = 1.00, p = 0.19) showed a significant impact on outcomes. Model discrimination was modest (C-index = 0.61, SE = 0.05). Prognostic impact of clinical and treatment variables on PFS The age, ECOG PS and BMI showed no significant associations with PFS (age HR = 1.00, p = 0.75; ECOG PS HR = 0.89, p = 0.69; BMI HR = 0.98, p = 0.54) and had no discriminative ability (C-index = 0.50, SE = 0.04). A higher number of metastatic locations was significantly associated with shorter PFS (HR = 1.43, 95% CI: 1.09–1.88, p = 0.01), whereas lesion size had no effect (HR = 1.00, p = 0.94). Model accuracy was modest (C-index = 0.58, SE = 0.05). There was no impact of radiotherapy (HR = 1.55, p = 0.17) or chemotherapy regimen (HR = 0.75, p = 0.38) on PFS, with limited predictive accuracy (C-index = 0.54, SE = 0.04 Immune-related adverse events irAEs were observed in 33 patients (37.08%), with 43 total events, including irAE recurrences in 6 patients. The most common irAEs were endocrine toxicities (14 patients, 42,4%), primarily affecting the thyroid gland. Hematologic and cutaneous irAEs were each reported in 8 cases (18.6%), hepatic in 12 cases (27.9%), while pulmonary toxicity occurred in one patient (2.3%). Most irAEs were mild to moderate in severity, but 18.6% of the cases were grade 3 or 4 toxicities. A detailed summary of first-occuring irAEs by type and grade is presented in Table 2 . Table 2 Summary of first-occurring immune-related adverse events Type of irAE Patients, n (%) Grade 1 Grade 2 Grade 3 Grade 4 Missing data Endocrine 12 (36.4) 3 7 1 — 1 Hematologic 4 (12.1) 2 1 — 1 — Pulmonary 1 (3) 1 — — — — Cutaneous 8 (24.2) 1 2 2 1 2 Hepatic 8 (24.2) 3 2 3 — — Total of irAE 33 (100%) — — — — — Abbreviation: irAEs, immune-related adverse events. The median time to onset of complications was 2.0 months, ( 95% CI 2.0–3.0). In 11 patients, immunotherapy was discontinued due to AEs; however, 9 of them continued chemotherapy alone. Among the 6 patients in whom pembrolizumab treatment was resumed, irAEs recurred in all cases - primarily with mild severity (5 patients, 83.33%) and in only one case with severe intensity. Prognostic value of occurance immune-related adverse events The multivariate Cox regression model for PFS included two categorical variables: the occurrence of irAEs and corticosteroid therapy (n = 89, events = 49). Neither irAE occurrence (HR = 0.80, 95% CI: 0.39–1.65, p = 0.55) nor corticosteroid use (HR = 1.22, 95% CI: 0.49–3.00, p = 0.67) significantly influenced PFS. The predictive accuracy of this model was low (C-index = 0.52, SE = 0.04). Chemotherapy-related adverse events The most common trAEs were hematologic toxicities, including neutropenia in 40 (44.9%) patients, anemia in 35 (39.3%), and thrombocytopenia in 19 (21.4%). Severe toxicities occurred in only a few cases. A summary of trAEs is presented in Table 3 . Table 3 Summary of chemotherapy-related adverse events Adverse Event Patients n(%) Grade 1 Grade 2 Grade 3 Grade 4 Missing data Neutropenia 40 (44.9) 4 18 12 3 3 Alopecia 38(42.7) NR NR NR NR NR Anemia 35(39.3) 6 18 8 NR 3 Elevated liver enzymes 27(30.3) 11 12 4 NR - Thrombocytopenia 19(21.3) 6 3 8 2 - Nausea 8(9) 5 3 NR NR - Vomiting 5(5.6) 3 2 NR NR - Hypersensitivity reactions 5 (5.6) NR 3 NR NR 2 Diarrhea 3(3.4) 1 2 NR NR - Febrile neutropenia 0 - - - - - Abbreviation: NR, not reported. Due to chemotherapy-related complications, dose reductions of cytotoxic agents were implemented in 28 (31,5%) patients. In 8 (9%) patients, chemotherapy was discontinued; however, 50% (4) of them continued immunotherapy. Treatment discontinuation and subsequent therapies At data cut-off, treatment was completed in 58 patients, primarily due to disease progression (77.6%). Other reasons included treatment-related complications (8 patients, 15.4%), patient request (3 patients, 5.8%), physician decision (1 patient, 1.9%), and death (1 patient, 1.9%). 15 patients had died, 31 remained on treatment, and 39 had commenced subsequent lines of systemic therapy. Over two-thirds of patients who completed pembrolizumab therapy received at least one subsequent line of treatment (median: 1; IQR 1–2), with sacituzumab govitecan being the most frequently used second-line agent (21 patients, 63.64%). Disscusion Our RWD study demonstrated a mPFS slightly exceeding 9 months. OS data remain immature and should be interpreted with caution. AEs were predominantly mild to moderate in severity and rarely necessitated treatment discontinuation. An overall objective response was achieved in nearly half of the patients, while SD was observed in just over one-third. Tumor progression at the first radiological assessment was rare. Despite certain limitations, our data are unique as, to our knowledge, this is the first published RWD analysis evaluating pembrolizumab combined with chemotherapy in the first-line treatment of PD-L1-positive mTNBC. Moreover, the evaluated patient population was ICI-näive, a clinical scenario likely to become increasingly uncommon given the current standard of care in early stage TNBC [ 31 ]. In our real-world cohort, mPFS closely aligned with the KEYNOTE-355 result in the same PD-L1 subgroup [ 14 , 15 ]. OS data were immature (n = 15 events) and could not be robustly compared with the trial’s mature OS outcomes. Interestingly, our study demonstrated similar objective response rate (47.19% vs. 52.8%) and a higher proportion of SD (38.2% vs. 28.6%), with radiologic progression at first assessment observed in only 7.9% of patients suggesting comparable or possibly greater early disease control. The incidence of immune-related adverse events was higher in our series (37.1%), grade ≥ 3 irAEs occurred in approximately one-third of affected patients, exceeding the proportion reported in KEYNOTE-355 [ 14 , 15 ]. These differences may reflect variations in patient selection, baseline characteristics, PD-L1 assay distribution, chemotherapy backbone use (notably, our greater proportion receiving gemcitabine–carboplatin), follow-up duration, and AE reporting practices. Importantly, despite these contextual differences, our PFS results in the CPS ≥ 10 population corroborate the pivotal trial’s findings, supporting the effectiveness of pembrolizumab plus chemotherapy in routine clinical practice. All published meta-analyses and systematic reviews evaluating the addition of ICIs to chemotherapy consistently confirm that combining ICI with chemotherapy improves PFS and OS in patients with PD-L1–positive mTNBC, while also increasing treatment-related toxicity [ 18 , 19 , 21 , 22 ]. The efficacy of ICIs appears to be unaffected by patient age [ 19 , 21 ], race, or ECOG PS [ 19 ]. Unlike our study, which identified only one clinical prognostic factor - a higher number of metastatic locations, which was significantly associated with shorter PFS - the aforementioned reviews highlighted specific clinical parameters associated with more favorable outcomes. These include the absence of prior chemotherapy and the site of metastatic disease - patients with lung and bone metastases derived the greatest benefit. [ 19 , 21 ] Conversely, no benefit was observed in patients with liver or central nervous system (CNS) metastases [ 19 , 21 ]. The lack of significant clinical prognostic indicators in our cohort could result from stringent eligibility criteria and limited variability in patient characteristics. RWD on the use of first-line pembrolizumab in patients with PD-L1-positive (CPS ≥ 10) mTNBC are currently lacking. Existing reports frequently describe ICI use collectively, without stratifying by PD-L1 expression or line of therapy. For instance, in the study by Zhang et al., more than half of the patients received ICIs in the second or later lines of treatment, with no stratification by PD-L1 status [ 24 ]. In contrast, the study by Qian et al. evaluated ICI efficacy across various breast cancer subtypes and treatment lines, reporting the most favorable outcomes when ICIs were administered in the first-line setting [ 25 ]. Notably, both studies identified similar adverse prognostic factors associated with poorer outcomes, including later-line therapy (vs. first-line), ECOG PS ≥ 1, liver metastases, and multiple metastatic sites [ 24 , 25 ]. In our analysis, the only clinical factor significantly associated with shorter PFS was a higher number of metastatic locations, whereas other reported predictors were not confirmed, likely due to differences in patient selection and methodological approaches. Nevertheless, our observation of longer OS in patients with prolonged intervals between radical treatment and metastatic relapse could indicate a biologically distinct, less aggressive cancer subtype. Future prospective studies should validate the prognostic significance of the disease-free interval as a potential surrogate biomarker for tumor biology and immunogenicity. Mechanisms underlying the enhanced clinical response to combined immunotherapy and chemotherapy is modulation of the tumor microenvironment (TME) [ 4 ]. Certain chemotherapeutic agents - particularly cisplatin and doxorubicin - can induce immunogenic cell death (ICD), resulting in the release of tumor-associated antigens, recruitment of dendritic cells (DCs), and activation of cytotoxic T lymphocytes [ 32 ]. This process increases T cell infiltration into tumors, effectively converting “cold” tumors into “hot” tumors and thereby enhancing responsiveness to ICIs [ 5 , 6 , 32 ]. In our study, most patients received carboplatin with gemcitabine, reflecting current local therapeutic preferences, though evidence regarding their immunomodulatory potential remains limited. The TONIC trial indicated superior immunomodulatory effects with short-term, low-dose doxorubicin or cisplatin chemotherapy compared to paclitaxel or cyclophosphamide [ 32 ]. Thus, future investigations should explore chemotherapy regimen selection to optimize the immune response in mTNBC. These considerations have prompted interest in novel therapeutic approaches, such as antibody–drug conjugates (ADCs). Sacituzumab govitecan, have been shown to induce ICD and may synergize with ICIs like pembrolizumab. This biological rationale was confirmed in the ASCENT-04 trial, where the combination of sacituzumab govitecan and pembrolizumab demonstrated superiority over standard chemotherapy plus pembrolizumab in previously untreated patients with PD-L1–positive mTNBC (CPS ≥ 10) [ 33 ]. The trial reported a mPFS of 11.2 months versus 7.8 months (hazard ratio [HR] = 0.65, p = 0.0009). and a median duration of response of 16.5 versus 9.2 months. In our cohort, the mPFS exceeded that reported for the control arm of ASCENT-04, suggesting potentially more durable responses; however, cross-trial comparisons should be interpreted with caution due to differences in patient populations and study design. Notably, the combination of sacituzumab govitecan and pembrolizumab was associated with a lower rate of treatment discontinuation due to adverse events (12% vs. 31%) [ 33 ]. These findings suggest the emergence of a potential new standard of care for first-line treatment in this challenging patient population. In the coming years, we anticipate rapid developments in immunotherapy and targeted treatments for TNBC. Particularly promising will be combination strategies involving not only conventional chemotherapy but also novel monoclonal antibodies, ADCs, and targeted molecular inhibitors, all of which may synergistically enhance the immune response. Concurrent advancements in diagnostic technologies, such as circulating tumor DNA (ctDNA) analysis and advanced imaging methods, will facilitate more precise monitoring of treatment responses, thereby enabling more accurate therapeutic decisions [ 34 – 37 ]. Our study provides important real-world evidence on the efficacy and safety of pembrolizumab combined with chemotherapy in Polish patients with PD-L1–positive metastatic TNBC, complementing the predominantly trial-based data currently available. By assessing outcomes in a uniformly ICI-naïve population treated under routine clinical conditions, our findings offer clinically relevant insights that can help oncologists anticipate the expected benefits and risks of this regimen in everyday practice. In this setting, most conventional clinical parameters showed limited prognostic value, with only the number of metastatic sites significantly associated with shorter PFS. While the interval from radical treatment to metastatic relapse did not reach statistical significance for PFS, the observed trend toward longer OS in patients with prolonged disease-free intervals may warrant further prospective evaluation as a potential surrogate of tumor biology. These results highlight the importance of integrating biomarker-driven approaches and tumor biology considerations into patient selection, moving beyond reliance on traditional clinical factors alone. Study limitations Our study has several limitations. Firstly, the retrospective design, relatively small sample size, and potential selection bias limit the strength of causal inferences. The absence of centralized PD-L1 (CPS) testing may have introduced inter-laboratory variability, potentially affecting comparability with standardized clinical trials. In addition, molecular and immune biomarkers such as TMB or inflammatory indices, which could provide further prognostic or predictive information, were not evaluated. Retrospective data collection also carries the risk of incomplete documentation of adverse events, which may have led to underreporting of treatment-related toxicities. Socio-demographic factors, including socioeconomic status, ethnicity, and healthcare access, were not analyzed despite their potential impact on outcomes. Our analysis was conducted within the framework of a national drug reimbursement program, whose eligibility criteria closely mirrored those of the KEYNOTE-355 trial. As a result, the study population was restricted to patients with CPS ≥ 10 and good performance status, which may limit the generalizability of the findings to the broader mTNBC population in Poland. The relatively uniform baseline characteristics may also have reduced the ability to detect additional clinical prognostic factors, which could explain why only the number of metastatic sites emerged as statistically significant in multivariate analysis. Although adverse events and tumor responses were evaluated according to standardized criteria (CTCAE v5.0, RECIST 1.1), assessments were performed across multiple centers by different clinicians and radiologists, potentially introducing variability related to local practice differences. Finally, the relatively short median follow-up and low number of OS events resulted in immature survival data, limiting conclusions regarding long-term outcomes, particularly OS. Conclusions In this first multicenter real-world analysis of pembrolizumab plus chemotherapy for PD-L1–positive mTNBC, mPFS exceeded 9 months, with early disease control rates comparable to KEYNOTE-355 and numerically higher than in the control arm of ASCENT-04 (cross-trial comparison). A higher number of metastatic sites was the only factor independently associated with shorter PFS; irAEs were frequent but rarely treatment-limiting and showed no prognostic impact. These findings confirm the regimen’s effectiveness and manageable safety in routine practice, while underscoring the need for biological and molecular markers to refine prognostication. Considering the increasing use of perioperative pembrolizumab and the likely introduction of first-line sacituzumab govitecan plus pembrolizumab, these results represent not only the first multicenter real-world analysis of this regimen but may also remain unique in the future, as such a patient population may no longer be available. Declarations Ethics approval and consent to participate This retrospective analysis was reviewed and approved by the Ethics Committee of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw Branch, Poland (approval reference number 51/2025, dated May 29, 2025). The committee authorized retrospective data collection regarding the effectiveness and safety outcomes of pembrolizumab-based treatment for mTNBC from all oncology centers involved in the study. All activities involving human subjects adhered strictly to ethical guidelines established by the institutional ethics committee, in alignment with the principles described in the Declaration of Helsinki (1964) and its subsequent amendments or comparable ethical standards. Written informed consent was obtained from each patient prior to the initiation of pembrolizumab therapy under the national reimbursement program, consistent with institutional procedures. The Ethics Committee waived the requirement for separate informed consent specifically for retrospective data collection. All study procedures fully complied with relevant ethical regulations and guidelines. Consent for publication Not applicable. Author Contributions Małgorzata Pieniążek designed and conceptualized the research. All authors were actively involved in organizing the database or collecting patient data. Jakub Wronowicz led all the statistical analyses. Małgorzata Pieniążek and Jakub Wronowicz interpreted the results. Ethical approval was obtained through the collaborative efforts of Miroslawa Püsküllüoğlu. Małgorzata Pieniążek wrote the initial draft of the manuscript, which was revised and commented by all the authors. The final version was approved by all the authors. Acknowledgements None. Funding No financial support was provided for the preparation of this manuscript.Funding for APC publication of this article was from Wroclaw Medical Univeristy. Conflict of interests Małgorzata Pieniążek travel grants and lecture fees from Pfizer, Novartis, Elli Lilly, MSD and Astra Zeneca; lecture fees from Gilead, Egis and Amgen, Aleksandra Konieczna travel grants and lecture fees from Pfizer, Novartis, Eli Lilly, MSD, AstraZeneca, Gilead; advisory board from Novartis, Roman Dubiański declares advisory board: Novartis, lectures and travel grants: Astra Zeneca, Novartis, Eli Lilly, Swixx, Gilead, MSD; lectures: Roche, Amgen, Egis, Pfizer, Merck. , Karolina Winsko-Szczęsnowicz travel grants and lecture fees from Roche, Eli Lilly, Novartis, Pfizer, Gilead, MSD, Aurovitas, Agnieszka Roman travel grants and lecture fees from Gilead, Pfizer MSD, lecture fees from Gilead, Novartis, AstraZeneca., Justyna Żubrowska travel grants and lecture fees from MSD, Novoartis, AstraZeneca; lecture fees from Pfizer, Swixx Biopharma, Lilly., Tomasz Ciszewski travel grants and lecture fees from Pfizer, Novartis, Eli Lilly, MSD, Roche, Gilead and AstraZeneca; , Natalia Cichowska-Cwalińska travel grants and lecture fees from Novartis, Renata Pacholczak-Madej travel grants from Accord, BMS, MSD, lecture fees from AstraZeneca, BMS, MSD, GSK, Novartis, Roche, Anna Górniak travel grants from Roche and Novartis, Joanna Pleskacz travel grants from BMS, MSD, Amgen, Novartis; lecture fees from Novartis, Pierre Fabre, Bogumiła Czartoryska-Arłukowicz: travel grants and lecture fees from Eli Lilly, Novartis, Pfizer, Astra, Gilead, Roche, Michał Jarząb conference fees by Gilead, Roche, speaker’s honoraria by Novartis, Roche, Lilly, Pfizer, Teva, Exact Sciences, Mammotome, advisory boards by Novartis, Pfizer;, Marek Jasiówka lecture fees from GSK, MSD, BMS, Roche and AstraZeneca; Aleksandra Łacko reports travel grants and lecture honoraria from Astra Zeneca, Pfizer, Novartis, Eli Lilly, Roche, Gilead Science including advisory board member role; Małgorzata Meluch: lectures fees: Novartis, Astra Zeneca, Lilly, Pfizer, Roche, support for conference attendance: Lilly, international training programs: Lilly, Novartis, Pfizer , Mirosława Püsküllüoğlu received travel grants and lecture honoraria from AstraZeneca, Roche, Novartis, Eli Lilly, Janssen, Gilead, and Amgen. Katarzyna Świderska, Iwona Danielewicz, Ewa Wójcik, Wioleta Łabul, Jakub Wronowicz report no conflicts of interest. Supplemental material Supplemental material for this article is available online. References Liu C, Yang M, Zhang D, Chen M, Zhu D (2022) Clinical cancer immunotherapy: Current progress and prospects. Front Immunol. https://doi.org/10.3389/fimmu.2022.961805 Sordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez-Rodriguez AP, Martínez-Pérez A, Rodrigo JP, García-Pedrero JM, Gonzalez S (2023) Chemo-Immunotherapy: A New Trend in Cancer Treatment. Cancers (Basel). https://doi.org/10.3390/cancers15112912 Mc Neil V, Lee SW (2025) Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies. Cancers (Basel). https://doi.org/10.3390/cancers17091408 Liu Y, Hu Y, Xue J, Li J, Yi J, Bu J, Zhang Z, Qiu P, Gu X (2023) Advances in immunotherapy for triple-negative breast cancer. Mol Cancer. https://doi.org/10.1186/s12943-023-01850-7 Geurts V, Kok M (2023) Immunotherapy for Metastatic Triple Negative Breast Cancer: Current Paradigm and Future Approaches. Curr Treat Options Oncol 24:628–643 Sriramulu S, Thoidingjam S, Speers C, Nyati S (2024) Present and Future of Immunotherapy for Triple-Negative Breast Cancer. Cancers (Basel). https://doi.org/10.3390/cancers16193250 Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Journal of Clinical Investigation 121:2750–2767 Lehmann BD, Jovanović B, Chen X, Estrada M V., Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA (2016) Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One. https://doi.org/10.1371/journal.pone.0157368 Grinda T, Antoine A, Jacot W, et al (2023) Real-world clinical and survival outcomes of patients with early relapsed triple-negative breast cancer from the ESME national cohort. Eur J Cancer. https://doi.org/10.1016/j.ejca.2023.05.023 Kesireddy M, Elsayed L, Shostrom VK, Agarwal P, Asif S, Yellala A, Krishnamurthy J (2024) Overall Survival and Prognostic Factors in Metastatic Triple-Negative Breast Cancer: A National Cancer Database Analysis. Cancers (Basel). https://doi.org/10.3390/cancers16101791 Schmid P, Adams S, Rugo HS, et al (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine 379:2108–2121 Emens LA, Adams S, Barrios CH, et al (2021) First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Annals of Oncology 32:983–993 Miles D, Gligorov J, André F, et al (2021) Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Annals of Oncology 32:994–1004 Cortes J, Rugo HS, Cescon DW, et al (2022) Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine 387:217–226 Cortes J, Cescon DW, Rugo HS, et al (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet 396:1817–1828 Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, et al (2024) 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. https://doi.org/10.1016/J.BREAST.2024.103756 Gennari A, André F, Barrios CH, et al (2021) ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Annals of Oncology 32:1475–1495 Qi Y, Yan X, Wang C, Cao H, Liu G (2022) Predictive value of PD-L1 expression to the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer: A systematic review and meta-analysis. Front Pharmacol. https://doi.org/10.3389/fphar.2022.1004821 Villacampa G, Tolosa P, Salvador F, Sánchez-Bayona R, Villanueva L, Dienstmann R, Ciruelos E, Pascual T (2022) Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in first-line metastatic triple-negative breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. https://doi.org/10.1016/j.ctrv.2022.102352 Wu Q, Wu C, Xie X (2023) Efficacy and Safety of Immune Checkpoint Inhibitors in Triple-negative Breast Cancer: A Study Based on 41 Cohorts Incorporating 6558 Participants. Journal of Immunotherapy 46:29–42 Yang J, Liu C, Guo Y, Guo W, Wu X (2024) Addition of PD-1/PD-L1 inhibitors to chemotherapy for triple-negative breast cancer: a meta-analysis. Front Oncol. https://doi.org/10.3389/fonc.2024.1309677 Liang X, Chen X, Li H, Li Y (2023) Immune checkpoint inhibitors in first-line therapies of metastatic or early triple-negative breast cancer: a systematic review and network meta-analysis. Front Endocrinol (Lausanne). https://doi.org/10.3389/fendo.2023.1137464 Skinner KE, Haiderali A, Huang M, Schwartzberg LS, Skinner KE (2021) Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer. Future Oncology 17:931–941 Zhang Z, Zhang Y, Liu C, et al (2023) A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer. Cancer Innovation 2:172–180 Qian X, Tao Y, Chen H, Li X, Wang Y, Xu X, Li S, Chen H, Cang S, Liu Y (2025) Real-world evaluation of the efficacy of immune checkpoint inhibitors in the treatment of metastatic breast cancer. Oncol Lett. https://doi.org/10.3892/ol.2024.14775 Notice of the Minister of Health of the Republic of Poland, dated 20 June 2023, concerning the list of reimbursed medicinal products, foods for special medical purposes, and medical devices, effective as of 1 July 2023. In: Internet. https://www.gov.pl/web/zdrowie/obwieszczenie-ministra-zdrowia-z-dnia-20-czerwca-2023-r-w-sprawie-wykazu-lekow-refundowanych-srodkow-spozywczych-specjalnego-przeznaczenia-zywieniowego-oraz-wyrobow-medycznych-na-1-lipca-2023-r?utm_source=chatgpt.com. Accessed 26 Jul 2025 Cortes J, Cescon DW, Rugo HS, et al (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet 396:1817–1828 Eisenhauer EA, Therasse P, Bogaerts J, et al (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247 Pembrolizumab - Summary of Product Characteristics. In: Internet. https://www.ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf. Accessed 26 Jul 2025 Cancer Institute N (2017) Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Loibl S, André F, Bachelot T, et al (2023) Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up†. Annals of Oncology. https://doi.org/10.1016/j.annonc.2023.11.016 Voorwerk L, Slagter M, Horlings HM, et al (2019) Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med 25:920–928 Tolaney SM, de Azambuja E, Kalinsky K, et al (2025) Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2025.43.17_SUPPL.LBA109 Bidard F-C, Mayer EL, Park YH, et al (2025) First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. New England Journal of Medicine. https://doi.org/10.1056/NEJMOA2502929 Thompson JC, Scholes DG, Carpenter EL, Aggarwal C (2023) Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors. British Journal of Cancer 2023 129:12 129:1893–1902 Kubeczko M, Polakiewicz-Gilowska A, D’Amico A, Chrabański O, Świderska K, Chmielik E, Blamek S, Handkiewicz-Junak D, Jarząb M (2024) The role of FDG PET assessment in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 inhibitors in the second-line setting. Front Oncol. https://doi.org/10.3389/FONC.2024.1454844 Filippi L, Urso L, Ferrari C, Guglielmo P, Evangelista L (2024) The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective. Eur J Nucl Med Mol Imaging 52:263 Additional Declarations No competing interests reported. Supplementary Files SupplementaryAppendixpembro.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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11:05:52","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":148785,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7367639/v1/1feddb9c4b5dfa1ffc074146.html"},{"id":91981295,"identity":"73b9630c-3624-4adf-aa35-f75bd276eb15","added_by":"auto","created_at":"2025-09-23 11:05:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":115172,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival in patients with metastatic \u003cem\u003ede novo\u003c/em\u003e and recurrent disease (preliminary data)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u003c/em\u003e: OS, overall survival.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7367639/v1/ae1d407cf80e2526d5338e02.png"},{"id":91981298,"identity":"7a67b8b5-0986-4cc6-af1b-b9680602a499","added_by":"auto","created_at":"2025-09-23 11:05:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122589,"visible":true,"origin":"","legend":"\u003cp\u003eProgression free survival in patients with metastatic \u003cem\u003ede novo\u003c/em\u003e and recurrent disease\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u003c/em\u003e: PFS, progression-free survival.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7367639/v1/3f79c9b4c5e35e7f1cdafef7.png"},{"id":104874205,"identity":"8a6166f1-98b0-4266-8c96-401b180b2e0f","added_by":"auto","created_at":"2026-03-18 08:29:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1102873,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7367639/v1/55f3ccc9-4d5c-4e9d-a128-39c483e288bd.pdf"},{"id":91981297,"identity":"f6e13696-e10c-453a-abf1-9568caba6cc0","added_by":"auto","created_at":"2025-09-23 11:05:52","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":21080,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryAppendixpembro.docx","url":"https://assets-eu.researchsquare.com/files/rs-7367639/v1/d397d42303f9268364abf684.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"First real-world experience with 1L pembrolizumab and chemotherapy treatment for advanced triple-negative breast cancer in Poland: safety analysis and first survival outcomes from a multicenter cohort","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmunotherapy using anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies, alone or in combination with chemotherapy, has significantly improved outcomes in many advanced solid tumors [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although historically breast cancer has been considered immunologically \"cold,\" triple-negative breast cancer (TNBC) - a distinct molecular subtype - has emerged as a promising candidate for immune-based therapeutic approaches [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This potential arises primarily from its higher levels of tumor-infiltrating lymphocytes (TILs), increased PD-L1 expression, and elevated tumor mutational burden (TMB) compared to other breast cancer subtypes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Advances in genomic profiling have also identified immune-enriched basal-like tumors that may be particularly responsive to immunotherapy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe aggressive course of metastatic TNBC (mTNBC) and the limited survival benefit of standard chemotherapy underscore the need for improved treatments [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Phase III trials have shown that adding immunotherapy to chemotherapy can provide clinical benefit, particularly in PD-L1-positive disease. In IMpassion130, atezolizumab plus nab-paclitaxel significantly improved progression-free survival (PFS) in PD-L1-positive patients, with a clinically meaningful but not statistically significant overall survival (OS) gain [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, IMpassion131, using standard paclitaxel, showed no PFS improvement [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Further evidence from KEYNOTE-355 demonstrated that pembrolizumab plus chemotherapy significantly improved both PFS and OS in patients with PD-L1\u0026ndash;positive mTNBC (Combined Positive Score [CPS]\u0026thinsp;\u0026ge;\u0026thinsp;10) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], establishing it as a standard first-line treatment option [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMeta-analyses confirm that chemoimmunotherapy improves PFS and shows a trend toward OS benefit in PD-L1\u0026ndash;positive mTNBC, with limited effect in PD-L1\u0026ndash;negative disease [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Pembrolizumab plus chemotherapy appears to have broader efficacy in the intention-to-treat population, whereas atezolizumab benefits are largely confined to PD-L1\u0026ndash;positive patients [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Despite strong trial evidence, real-world data (RWD) for pembrolizumab in this setting are lacking. Available RWD suggest that first-line immune checkpoint inhibitor (ICI) use yields better outcomes than later lines, emphasizing the importance of treatment timing [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn Poland, pembrolizumab has been reimbursed within the Ministry of Health drug program since July 2023 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], making evaluation of its real-world effectiveness and safety highly relevant. The primary aim of this study was to assess PFS and OS, and describe adverse events (AEs), in patients treated with pembrolizumab plus chemotherapy. We also sought to identify factors associated with outcomes, including time from radical treatment to metastatic relapse, time from relapse to systemic therapy initiation, and baseline clinical characteristics.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eStudy population and treatment\u003c/p\u003e\u003cp\u003eBetween September 2022 and February 2025, pembrolizumab combined with chemotherapy was initiated in 89 female patients diagnosed with advanced TNBC across thirteen oncology centers in Poland (listed in Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e - Supplementary Appendix). Patients were identified via hospital databases and the Polish National Health Fund registry system. Inclusion criteria followed the Polish drug reimbursement guidelines based on the KEYNOTE-355 trial protocol [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], requiring histologically confirmed TNBC according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) standards, confirmed PD-L1 positivity (CPS\u0026thinsp;\u0026ge;\u0026thinsp;10) assessed by a validated assay, and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Additionally, patients had to exhibit inoperable or metastatic disease, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0\u0026ndash;1, sufficient organ function, no active metastases in the central nervous system, and no previous systemic treatment for advanced disease or at least six months relapsed since completion of prior curative-intent therapy. Treatment was discontinued at the time of progressive disease, unacceptable toxicity, deterioration of performance status or quality of life, or upon decision by the patient or treating physician. A comprehensive description of inclusion and exclusion criteria aligned with Polish reimbursement regulations is provided in the Supplementary Appendix. Patients receiving pembrolizumab under a different funding method (outside clinical trials) were also eligible for inclusion.\u003c/p\u003e\u003cp\u003ePembrolizumab was administered intravenously at doses of either 200 mg every three weeks or 400 mg every six weeks, according to physician preference. The chemotherapy regimen was selected individually by the treating oncologist, consistent with recommendations outlined in the European Union Summary of Product Characteristics (SmPC), including paclitaxel administered intravenously at 90 mg/m\u0026sup2; body surface area on days 1, 8, and 15 every 28 days, or gemcitabine at 1000 mg/m\u0026sup2; body surface area combined with carboplatin (AUC 2 mg/mL/min) on days 1 and 8 every 21 days [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. AEs were monitored and graded following the National Cancer Institute\u0026rsquo;s Common Terminology Criteria for AEs (NCI-CTCAE), version 5.0 [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Modifications to treatment doses following AEs were implemented based on recommendations from the SmPC [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Treatment efficacy was evaluated every three months by chest, abdomen or pelvis imaging (mostly using computed tomography (CT) or in special clinical situations magnetic resonance imaging (MRI)) according to RECIST, version 1.1 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eData collection\u003c/p\u003e\u003cp\u003eData were collected retrospectively using information extracted from both electronic and paper medical records with cut-off on August 5, 2025. To ensure clarity and completeness, the dataset was organized into multiple categories. Demographic data included patient age at the time of diagnosis and at initiation of palliative systemic therapy. Pathological parameters comprised human epidermal growth factor receptor 2 (HER2) expression, histological grade, and the Ki-67 proliferation index, assessed using either the initial diagnostic material or the most recent biopsy available.\u003c/p\u003e\u003cp\u003eClinical characteristics included the date of diagnosis of mTNBC, the extent of disease dissemination (defined by the number of metastatic sites, count of measurable lesions, and size of the largest lesion) and patient-related factors such as ECOG PS and body mass index (BMI) at therapy onset. Information regarding the type and intent of initial treatment (curative or palliative), the date of completion of systemic radical approach, and the time point of disease progression to metastatic stage was also collected.\u003c/p\u003e\u003cp\u003eTreatment-related variables focused on pembrolizumab-based therapy, including the start date, type of chemotherapy (paclitaxel or carboplatin with gemcitabine), and date of the last administered dose. Details regarding chemotherapy dose adjustments and any concurrent radiotherapy were also captured.\u003c/p\u003e\u003cp\u003eAEs associated with both immunotherapy and chemotherapy were documented according to severity using the NCI-CTCAE version 5.0 criteria, along with the use of corticosteroids when clinically indicated for AE management. The dataset further included details on subsequent lines of therapy following pembrolizumab-based treatment, information on the timing of the last clinical assessment and, if applicable, the date of death.\u003c/p\u003e\u003cp\u003ePrimary and secondary objectives\u003c/p\u003e\u003cp\u003eThe primary objective of this study was to evaluate PFS, OS, and to characterize AEs in a real-world Polish cohort of women diagnosed with mTNBC and PD-L1 expression (CPS\u0026thinsp;\u0026ge;\u0026thinsp;10), treated with pembrolizumab in combination with chemotherapy. OS was defined as the time from initiation of pembrolizumab-based treatment to death from any cause, while PFS was defined as the time from treatment initiation to documented disease progression or death, whichever occurs first.\u003c/p\u003e\u003cp\u003eThe secondary objectives focus on identifying clinical, patient-, disease-, and treatment-related factors that may be associated with PFS and OS. Specifically, the study investigates whether the duration between completion of radical treatment and the onset of metastatic disease, as well as the time from diagnosis of metastatic relapse to initiation of systemic therapy, correlate with survival outcomes. Patient-related characteristics such as age at treatment initiation, baseline ECOG PS, and BMI are also analyzed for potential associations with PFS and OS.\u003c/p\u003e\u003cp\u003eAdditionally, disease-related features including the number of metastatic sites, the number of measurable lesions, the size of the largest lesion, and overall measurable tumor burden are examined for their prognostic value. Treatment-related factors were explored as well, including the type of chemotherapy regimen administered (paclitaxel, carboplatin, or carboplatin combined with gemcitabine), any reductions in chemotherapy dose, and the use of radiotherapy during treatment.\u003c/p\u003e\u003cp\u003eFinally, the study evaluated the impact of immune-related AEs (irAEs) on clinical outcomes, specifically assessing whether the occurrence and severity of irAEs influence PFS and OS, and whether the use of corticosteroids for irAE management affects treatment efficacy. Treatment-related AE (trAEs) and irAEs were assessed as in the clinical trial setting, that is, based on the treating physician\u0026rsquo;s individual judgment.\u003c/p\u003e\u003cp\u003e The Ethics Committee of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw Branch, Poland, reviewed and approved this retrospective analysis (approval no. 51/2025, issued on May 29, 2025).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were summarized using medians and interquartile ranges (IQR, 1st\u0026ndash;3rd quartiles), as their distributions for both PFS and OS significantly deviated from normality (Shapiro-Wilk test). Categorical variables were described using frequencies and percentages. The selection of variables for correlation and regression analyses was based on clinical relevance, expert opinion, and previously published evidence.\u003c/p\u003e\u003cp\u003eThe association between explanatory variables and PFS or OS was assessed using multivariate Cox proportional hazards regression models. Variables for inclusion were primarily selected according to prior research findings. For PFS, separate initial Cox models were built for three domains: (1) clinical characteristics, (2) disease burden, and (3) treatment-related factors.\u003c/p\u003e\u003cp\u003eIn the disease burden model (n\u0026thinsp;=\u0026thinsp;79, events\u0026thinsp;=\u0026thinsp;45), the initial set of variables comprised number of metastatic lesion locations, number of measurable lesions, tumor burden, and size of the largest lesion. Due to violations of the proportional hazards assumption, number of measurable lesions and tumor burden were removed. The final adjusted model retained number of metastatic lesion locations and size of the largest lesion.\u003c/p\u003e\u003cp\u003eIn the treatment-related model (n\u0026thinsp;=\u0026thinsp;87, events\u0026thinsp;=\u0026thinsp;48), the initial variables were radiotherapy, chemotherapy dose reduction and chemotherapy regimen. Chemotherapy dose reduction violated the proportional hazards assumption and was excluded.\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier analyses demonstrated crossing survival curves for both OS and PFS; therefore, the Peto\u0026ndash;Peto log-rank test, which does not assume proportional hazards, was applied for group comparisons. All statistical analyses were performed using R (version 4.4.0) and Python (version 3.11.4), with statistical significance set at α\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline patient characteristics\u003c/p\u003e\u003cp\u003eClinical data were collected from 89 women treated with pembrolizumab-based therapy. The median age at initial diagnosis was 54 years (IQR: 45\u0026ndash;63), increasing to 58 years (IQR: 48\u0026ndash;67) at the start of systemic treatment. The majority of patients were postmenopausal and had at least one comorbid condition. A \u003cem\u003eBReast CAncer\u003c/em\u003e gene \u003cb\u003e(\u003c/b\u003e\u003cem\u003eBRCA\u003c/em\u003e) mutation was identified in approximately one-sixth of the cohort, while about one-quarter had not undergone genetic testing. PD-L1 expression, assessed by CPS, varied between centers. For 17 patients, the result was reported qualitatively as \u0026ldquo;\u0026gt;10\u0026rdquo;, whereas in the remaining cases (n\u0026thinsp;=\u0026thinsp;72) quantitative values were available, with a median CPS of 20 (IQR: 15\u0026ndash;50).\u003c/p\u003e\u003cp\u003eInvasive ductal carcinoma was the predominant histological subtype. Tumors exhibited aggressive features: most were classified as histological grade 3, and the median Ki-67 proliferation index was 70% (IQR: 40\u0026ndash;80).\u003c/p\u003e\u003cp\u003eMetastatic spread most commonly involved the lymph nodes and lungs. The median number of metastatic sites was 2 (IQR: 1\u0026ndash;3). The total sum of the largest dimensions of all measurable lesions in a CT scan performed prior to the initiation of the treatment had a median of 81.0 mm (IQR: 50.0\u0026ndash;132.8). The number of measurable lesions varied. A comprehensive summary of patient and disease characteristics is provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristic of patients and the disease\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber and Percentage (N\u0026thinsp;=\u0026thinsp;89 (100%))\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient Characteristics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMenopausal status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePremenopausal n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16(18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePerimenopausal n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11(12.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePostmenopausal n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61(68.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eComorbidities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36(40.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(59,6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBRCA mutation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot present n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55(61.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16(18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot tested n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18(20.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease Characteristics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHistological grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(59.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29(32.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLack of data n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(5.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHistological subtype\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInvasive ductal n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78(87.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMetaplastic n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6(6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInvasive lobular n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOthers n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHER-2 IHC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52(58.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(31.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003csup\u003e*\u003c/sup\u003e n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSite of metastatic disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLymph nodes n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56 (62.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLung n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (48.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBones n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (31.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLiver n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (22.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSkin/subcutaneous tissue n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (16.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMalignant effusion n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (13.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBrain n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOther n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (13,5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of measurable lesions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u0026ndash;3 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (39.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u0026ndash;10 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (32.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u0026ndash;20 n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;20 n(%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOnly non-measurable lesions n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (2,3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cem\u003eAbbreviation\u003c/em\u003e: BRCA, BReast CAncer gene; HER2, human epidermal growth factor receptor 2, IHC, immunohistochemistry\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e* Negative in situ hybridization (ISH) result\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTreatment exposure and outcomes\u003c/p\u003e\u003cp\u003eThe median follow-up was 10.1 months (IQR 5.5\u0026ndash;14.8). Most patients (62, 69.7%) received carboplatin combined with gemcitabine, while 26 (29.2%) were treated with paclitaxel. One patient received carboplatin monotherapy based on physician discretion. All patients were administered pembrolizumab at a dose of 200 mg intravenously every three weeks. Among those who completed treatment, the median number of pembrolizumab doses was 6 (IQR 5\u0026ndash;9) and the median treatment time was 5.5 months (IQR 3.7\u0026ndash;9.9).\u003c/p\u003e\u003cp\u003eThe best treatment response was partial response (PR) in 39 (43.8%) patients and complete response (CR) in 3 ((3.4%). Stable disease (SD) was observed in 34 (38.2%) patients. Response data were unavailable for 6 (6.7%) individuals. Notably, only 7 (7.9%) patients showed tumor progression at the first radiological assessment.\u003c/p\u003e\u003cp\u003eSurvival outcomes\u003c/p\u003e\u003cp\u003eOS data were immature due to the low number of events (n\u0026thinsp;=\u0026thinsp;15; 16.9%). Preliminary observations suggest a possible trend toward longer OS in patients treated with curative intent in the past compared with patients diagnosed with \u003cem\u003ede novo\u003c/em\u003e metastatic BC. For those, who died, OS ranged from 0.2 to 26.2 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMedian PFS (mPFS) was 9.3 months (95% CI: 6.6\u0026ndash;14.7). Subgroup analysis showed that patients with prior curative treatment (n\u0026thinsp;=\u0026thinsp;58; 65.2%) had mPFS of 7.2 months (95% CI: 5.8\u0026ndash;14.7), whereas data for patients with \u003cem\u003ede novo\u003c/em\u003e metastatic disease (n\u0026thinsp;=\u0026thinsp;31; 34.8%) remained immature (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePrognostic impact of time intervals on PFS\u003c/p\u003e\u003cp\u003eThe median interval between the end of radical treatment and the diagnosis of metastatic disease was 21.3 months (95% CI: 13.7\u0026ndash;27.2). The median interval from metastatic diagnosis to treatment initiation was 1.58 months (95% CI: 1.31\u0026ndash;1.94)\u003c/p\u003e\u003cp\u003eIn the multivariate analysis of PFS, neither the interval from the end of radical treatment to metastatic diagnosis (HR\u0026thinsp;=\u0026thinsp;1.00, p\u0026thinsp;=\u0026thinsp;0.36) nor the interval from metastatic diagnosis to treatment initiation (HR\u0026thinsp;=\u0026thinsp;1.00, p\u0026thinsp;=\u0026thinsp;0.19) showed a significant impact on outcomes. Model discrimination was modest (C-index\u0026thinsp;=\u0026thinsp;0.61, SE\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003ePrognostic impact of clinical and treatment variables on PFS\u003c/p\u003e\u003cp\u003eThe age, ECOG PS and BMI showed no significant associations with PFS (age HR\u0026thinsp;=\u0026thinsp;1.00, p\u0026thinsp;=\u0026thinsp;0.75; ECOG PS HR\u0026thinsp;=\u0026thinsp;0.89, p\u0026thinsp;=\u0026thinsp;0.69; BMI HR\u0026thinsp;=\u0026thinsp;0.98, p\u0026thinsp;=\u0026thinsp;0.54) and had no discriminative ability (C-index\u0026thinsp;=\u0026thinsp;0.50, SE\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e\u003cp\u003eA higher number of metastatic locations was significantly associated with shorter PFS (HR\u0026thinsp;=\u0026thinsp;1.43, 95% CI: 1.09\u0026ndash;1.88, p\u0026thinsp;=\u0026thinsp;0.01), whereas lesion size had no effect (HR\u0026thinsp;=\u0026thinsp;1.00, p\u0026thinsp;=\u0026thinsp;0.94). Model accuracy was modest (C-index\u0026thinsp;=\u0026thinsp;0.58, SE\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eThere was no impact of radiotherapy (HR\u0026thinsp;=\u0026thinsp;1.55, p\u0026thinsp;=\u0026thinsp;0.17) or chemotherapy regimen (HR\u0026thinsp;=\u0026thinsp;0.75, p\u0026thinsp;=\u0026thinsp;0.38) on PFS, with limited predictive accuracy (C-index\u0026thinsp;=\u0026thinsp;0.54, SE\u0026thinsp;=\u0026thinsp;0.04\u003c/p\u003e\u003cp\u003eImmune-related adverse events\u003c/p\u003e\u003cp\u003eirAEs were observed in 33 patients (37.08%), with 43 total events, including irAE recurrences in 6 patients. The most common irAEs were endocrine toxicities (14 patients, 42,4%), primarily affecting the thyroid gland. Hematologic and cutaneous irAEs were each reported in 8 cases (18.6%), hepatic in 12 cases (27.9%), while pulmonary toxicity occurred in one patient (2.3%). Most irAEs were mild to moderate in severity, but 18.6% of the cases were grade 3 or 4 toxicities. A detailed summary of first-occuring irAEs by type and grade is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of first-occurring immune-related adverse events\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of irAE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePatients, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMissing data\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (36.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematologic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePulmonary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCutaneous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (24.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (24.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal \u003cb\u003eof\u003c/b\u003e irAE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAbbreviation: irAEs, immune-related adverse events.\u003c/p\u003e\u003cp\u003eThe median time to onset of complications was 2.0 months, \u003cb\u003e(\u003c/b\u003e95% CI 2.0\u0026ndash;3.0).\u003c/p\u003e\u003cp\u003eIn 11 patients, immunotherapy was discontinued due to AEs; however, 9 of them continued chemotherapy alone. Among the 6 patients in whom pembrolizumab treatment was resumed, irAEs recurred in all cases - primarily with mild severity (5 patients, 83.33%) and in only one case with severe intensity.\u003c/p\u003e\u003cp\u003ePrognostic value of occurance immune-related adverse events\u003c/p\u003e\u003cp\u003eThe multivariate Cox regression model for PFS included two categorical variables: the occurrence of irAEs and corticosteroid therapy (n\u0026thinsp;=\u0026thinsp;89, events\u0026thinsp;=\u0026thinsp;49). Neither irAE occurrence (HR\u0026thinsp;=\u0026thinsp;0.80, 95% CI: 0.39\u0026ndash;1.65, p\u0026thinsp;=\u0026thinsp;0.55) nor corticosteroid use (HR\u0026thinsp;=\u0026thinsp;1.22, 95% CI: 0.49\u0026ndash;3.00, p\u0026thinsp;=\u0026thinsp;0.67) significantly influenced PFS. The predictive accuracy of this model was low (C-index\u0026thinsp;=\u0026thinsp;0.52, SE\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e\u003cp\u003eChemotherapy-related adverse events\u003c/p\u003e\u003cp\u003eThe most common trAEs were hematologic toxicities, including neutropenia in 40 (44.9%) patients, anemia in 35 (39.3%), and thrombocytopenia in 19 (21.4%). Severe toxicities occurred in only a few cases. A summary of trAEs is presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of chemotherapy-related adverse events\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse Event\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePatients n(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMissing data\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (44.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlopecia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38(42.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35(39.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated liver enzymes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27(30.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19(21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypersensitivity reactions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFebrile neutropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAbbreviation: NR, not reported.\u003c/p\u003e\u003cp\u003eDue to chemotherapy-related complications, dose reductions of cytotoxic agents were implemented in 28 (31,5%) patients. In 8 (9%) patients, chemotherapy was discontinued; however, 50% (4) of them continued immunotherapy.\u003c/p\u003e\u003cp\u003eTreatment discontinuation and subsequent therapies\u003c/p\u003e\u003cp\u003eAt data cut-off, treatment was completed in 58 patients, primarily due to disease progression (77.6%). Other reasons included treatment-related complications (8 patients, 15.4%), patient request (3 patients, 5.8%), physician decision (1 patient, 1.9%), and death (1 patient, 1.9%). 15 patients had died, 31 remained on treatment, and 39 had commenced subsequent lines of systemic therapy. Over two-thirds of patients who completed pembrolizumab therapy received at least one subsequent line of treatment (median: 1; IQR 1\u0026ndash;2), with sacituzumab govitecan being the most frequently used second-line agent (21 patients, 63.64%).\u003c/p\u003e"},{"header":"Disscusion","content":"\u003cp\u003eOur RWD study demonstrated a mPFS slightly exceeding 9 months. OS data remain immature and should be interpreted with caution. AEs were predominantly mild to moderate in severity and rarely necessitated treatment discontinuation. An overall objective response was achieved in nearly half of the patients, while SD was observed in just over one-third. Tumor progression at the first radiological assessment was rare. Despite certain limitations, our data are unique as, to our knowledge, this is the first published RWD analysis evaluating pembrolizumab combined with chemotherapy in the first-line treatment of PD-L1-positive mTNBC. Moreover, the evaluated patient population was ICI-n\u0026auml;ive, a clinical scenario likely to become increasingly uncommon given the current standard of care in early stage TNBC [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our real-world cohort, mPFS closely aligned with the KEYNOTE-355 result in the same PD-L1 subgroup [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. OS data were immature (n\u0026thinsp;=\u0026thinsp;15 events) and could not be robustly compared with the trial\u0026rsquo;s mature OS outcomes. Interestingly, our study demonstrated similar objective response rate (47.19% vs. 52.8%) and a higher proportion of SD (38.2% vs. 28.6%), with radiologic progression at first assessment observed in only 7.9% of patients suggesting comparable or possibly greater early disease control. The incidence of immune-related adverse events was higher in our series (37.1%), grade\u0026thinsp;\u0026ge;\u0026thinsp;3 irAEs occurred in approximately one-third of affected patients, exceeding the proportion reported in KEYNOTE-355 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These differences may reflect variations in patient selection, baseline characteristics, PD-L1 assay distribution, chemotherapy backbone use (notably, our greater proportion receiving gemcitabine\u0026ndash;carboplatin), follow-up duration, and AE reporting practices. Importantly, despite these contextual differences, our PFS results in the CPS\u0026thinsp;\u0026ge;\u0026thinsp;10 population corroborate the pivotal trial\u0026rsquo;s findings, supporting the effectiveness of pembrolizumab plus chemotherapy in routine clinical practice.\u003c/p\u003e\u003cp\u003eAll published meta-analyses and systematic reviews evaluating the addition of ICIs to chemotherapy consistently confirm that combining ICI with chemotherapy improves PFS and OS in patients with PD-L1\u0026ndash;positive mTNBC, while also increasing treatment-related toxicity [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The efficacy of ICIs appears to be unaffected by patient age [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], race, or ECOG PS [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Unlike our study, which identified only one clinical prognostic factor - a higher number of metastatic locations, which was significantly associated with shorter PFS - the aforementioned reviews highlighted specific clinical parameters associated with more favorable outcomes. These include the absence of prior chemotherapy and the site of metastatic disease - patients with lung and bone metastases derived the greatest benefit. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Conversely, no benefit was observed in patients with liver or central nervous system (CNS) metastases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The lack of significant clinical prognostic indicators in our cohort could result from stringent eligibility criteria and limited variability in patient characteristics.\u003c/p\u003e\u003cp\u003eRWD on the use of first-line pembrolizumab in patients with PD-L1-positive (CPS\u0026thinsp;\u0026ge;\u0026thinsp;10) mTNBC are currently lacking. Existing reports frequently describe ICI use collectively, without stratifying by PD-L1 expression or line of therapy. For instance, in the study by Zhang et al., more than half of the patients received ICIs in the second or later lines of treatment, with no stratification by PD-L1 status [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In contrast, the study by Qian et al. evaluated ICI efficacy across various breast cancer subtypes and treatment lines, reporting the most favorable outcomes when ICIs were administered in the first-line setting [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Notably, both studies identified similar adverse prognostic factors associated with poorer outcomes, including later-line therapy (vs. first-line), ECOG PS\u0026thinsp;\u0026ge;\u0026thinsp;1, liver metastases, and multiple metastatic sites [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our analysis, the only clinical factor significantly associated with shorter PFS was a higher number of metastatic locations, whereas other reported predictors were not confirmed, likely due to differences in patient selection and methodological approaches. Nevertheless, our observation of longer OS in patients with prolonged intervals between radical treatment and metastatic relapse could indicate a biologically distinct, less aggressive cancer subtype. Future prospective studies should validate the prognostic significance of the disease-free interval as a potential surrogate biomarker for tumor biology and immunogenicity.\u003c/p\u003e\u003cp\u003eMechanisms underlying the enhanced clinical response to combined immunotherapy and chemotherapy is modulation of the tumor microenvironment (TME) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Certain chemotherapeutic agents - particularly cisplatin and doxorubicin - can induce immunogenic cell death (ICD), resulting in the release of tumor-associated antigens, recruitment of dendritic cells (DCs), and activation of cytotoxic T lymphocytes [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This process increases T cell infiltration into tumors, effectively converting \u0026ldquo;cold\u0026rdquo; tumors into \u0026ldquo;hot\u0026rdquo; tumors and thereby enhancing responsiveness to ICIs [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In our study, most patients received carboplatin with gemcitabine, reflecting current local therapeutic preferences, though evidence regarding their immunomodulatory potential remains limited. The TONIC trial indicated superior immunomodulatory effects with short-term, low-dose doxorubicin or cisplatin chemotherapy compared to paclitaxel or cyclophosphamide [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Thus, future investigations should explore chemotherapy regimen selection to optimize the immune response in mTNBC.\u003c/p\u003e\u003cp\u003eThese considerations have prompted interest in novel therapeutic approaches, such as antibody\u0026ndash;drug conjugates (ADCs). Sacituzumab govitecan, have been shown to induce ICD and may synergize with ICIs like pembrolizumab. This biological rationale was confirmed in the ASCENT-04 trial, where the combination of sacituzumab govitecan and pembrolizumab demonstrated superiority over standard chemotherapy plus pembrolizumab in previously untreated patients with PD-L1\u0026ndash;positive mTNBC (CPS\u0026thinsp;\u0026ge;\u0026thinsp;10) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The trial reported a mPFS of 11.2 months versus 7.8 months (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;0.65, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0009). and a median duration of response of 16.5 versus 9.2 months. In our cohort, the mPFS exceeded that reported for the control arm of ASCENT-04, suggesting potentially more durable responses; however, cross-trial comparisons should be interpreted with caution due to differences in patient populations and study design. Notably, the combination of sacituzumab govitecan and pembrolizumab was associated with a lower rate of treatment discontinuation due to adverse events (12% vs. 31%) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. These findings suggest the emergence of a potential new standard of care for first-line treatment in this challenging patient population.\u003c/p\u003e\u003cp\u003eIn the coming years, we anticipate rapid developments in immunotherapy and targeted treatments for TNBC. Particularly promising will be combination strategies involving not only conventional chemotherapy but also novel monoclonal antibodies, ADCs, and targeted molecular inhibitors, all of which may synergistically enhance the immune response. Concurrent advancements in diagnostic technologies, such as circulating tumor DNA (ctDNA) analysis and advanced imaging methods, will facilitate more precise monitoring of treatment responses, thereby enabling more accurate therapeutic decisions [\u003cspan additionalcitationids=\"CR35 CR36\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur study provides important real-world evidence on the efficacy and safety of pembrolizumab combined with chemotherapy in Polish patients with PD-L1\u0026ndash;positive metastatic TNBC, complementing the predominantly trial-based data currently available. By assessing outcomes in a uniformly ICI-na\u0026iuml;ve population treated under routine clinical conditions, our findings offer clinically relevant insights that can help oncologists anticipate the expected benefits and risks of this regimen in everyday practice. In this setting, most conventional clinical parameters showed limited prognostic value, with only the number of metastatic sites significantly associated with shorter PFS. While the interval from radical treatment to metastatic relapse did not reach statistical significance for PFS, the observed trend toward longer OS in patients with prolonged disease-free intervals may warrant further prospective evaluation as a potential surrogate of tumor biology. These results highlight the importance of integrating biomarker-driven approaches and tumor biology considerations into patient selection, moving beyond reliance on traditional clinical factors alone.\u003c/p\u003e\u003cp\u003eStudy limitations\u003c/p\u003e\u003cp\u003eOur study has several limitations. Firstly, the retrospective design, relatively small sample size, and potential selection bias limit the strength of causal inferences. The absence of centralized PD-L1 (CPS) testing may have introduced inter-laboratory variability, potentially affecting comparability with standardized clinical trials. In addition, molecular and immune biomarkers such as TMB or inflammatory indices, which could provide further prognostic or predictive information, were not evaluated. Retrospective data collection also carries the risk of incomplete documentation of adverse events, which may have led to underreporting of treatment-related toxicities. Socio-demographic factors, including socioeconomic status, ethnicity, and healthcare access, were not analyzed despite their potential impact on outcomes.\u003c/p\u003e\u003cp\u003eOur analysis was conducted within the framework of a national drug reimbursement program, whose eligibility criteria closely mirrored those of the KEYNOTE-355 trial. As a result, the study population was restricted to patients with CPS\u0026thinsp;\u0026ge;\u0026thinsp;10 and good performance status, which may limit the generalizability of the findings to the broader mTNBC population in Poland. The relatively uniform baseline characteristics may also have reduced the ability to detect additional clinical prognostic factors, which could explain why only the number of metastatic sites emerged as statistically significant in multivariate analysis.\u003c/p\u003e\u003cp\u003eAlthough adverse events and tumor responses were evaluated according to standardized criteria (CTCAE v5.0, RECIST 1.1), assessments were performed across multiple centers by different clinicians and radiologists, potentially introducing variability related to local practice differences. Finally, the relatively short median follow-up and low number of OS events resulted in immature survival data, limiting conclusions regarding long-term outcomes, particularly OS.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this first multicenter real-world analysis of pembrolizumab plus chemotherapy for PD-L1\u0026ndash;positive mTNBC, mPFS exceeded 9 months, with early disease control rates comparable to KEYNOTE-355 and numerically higher than in the control arm of ASCENT-04 (cross-trial comparison). A higher number of metastatic sites was the only factor independently associated with shorter PFS; irAEs were frequent but rarely treatment-limiting and showed no prognostic impact. These findings confirm the regimen\u0026rsquo;s effectiveness and manageable safety in routine practice, while underscoring the need for biological and molecular markers to refine prognostication. Considering the increasing use of perioperative pembrolizumab and the likely introduction of first-line sacituzumab govitecan plus pembrolizumab, these results represent not only the first multicenter real-world analysis of this regimen but may also remain unique in the future, as such a patient population may no longer be available.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis was reviewed and approved by the Ethics Committee of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw Branch, Poland (approval reference number 51/2025, dated May 29, 2025). The committee authorized retrospective data collection regarding the effectiveness and safety outcomes of pembrolizumab-based treatment for mTNBC from all oncology centers involved in the study. All activities involving human subjects adhered strictly to ethical guidelines established by the institutional ethics committee, in alignment with the principles described in the Declaration of Helsinki (1964) and its subsequent amendments or comparable ethical standards. Written informed consent was obtained from each patient prior to the initiation of pembrolizumab therapy under the national reimbursement program, consistent with institutional procedures. The Ethics Committee waived the requirement for separate informed consent specifically for retrospective data collection. All study procedures fully complied with relevant ethical regulations and guidelines.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eMałgorzata Pieniążek designed and conceptualized the research. All authors were actively involved in organizing the database or collecting patient data. Jakub Wronowicz led all the statistical analyses. Małgorzata Pieniążek and Jakub Wronowicz interpreted the results. Ethical approval was obtained through the collaborative efforts of Miroslawa P\u0026uuml;sk\u0026uuml;ll\u0026uuml;oğlu. Małgorzata Pieniążek wrote the initial draft of the manuscript, which was revised and commented by all the authors. The final version was approved by all the authors.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo financial support was provided for the preparation of this manuscript.Funding for APC publication of this article was from Wroclaw Medical Univeristy.\u003c/p\u003e\n\u003cp\u003eConflict of interests\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMałgorzata Pieniążek travel grants and lecture fees from Pfizer, Novartis, Elli Lilly, MSD and Astra Zeneca; lecture fees from Gilead, Egis and Amgen, Aleksandra Konieczna\u003csup\u003e\u0026nbsp;\u003c/sup\u003etravel grants and lecture fees from Pfizer, Novartis, Eli Lilly, MSD, AstraZeneca, Gilead; advisory board from Novartis, Roman Dubiański\u003csup\u003e\u0026nbsp;\u003c/sup\u003edeclares\u003csup\u003e\u0026nbsp;\u003c/sup\u003eadvisory board: Novartis, lectures and travel grants: Astra Zeneca, Novartis, Eli Lilly, Swixx, Gilead, MSD; lectures: Roche, Amgen, Egis, Pfizer, Merck.\u003csub\u003e,\u003c/sub\u003e Karolina Winsko-Szczęsnowicz\u003cstrong\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003etravel grants and lecture fees from Roche, Eli Lilly, Novartis, Pfizer, Gilead, MSD, Aurovitas, Agnieszka Roman\u003csup\u003e\u0026nbsp;\u003c/sup\u003etravel grants and lecture fees from Gilead, Pfizer \u0026nbsp;MSD, lecture fees from Gilead, Novartis, AstraZeneca., Justyna Żubrowska\u003csup\u003e\u0026nbsp;\u003c/sup\u003e travel grants and lecture fees from MSD, Novoartis, AstraZeneca; lecture fees from Pfizer, Swixx Biopharma, Lilly., Tomasz Ciszewski\u003csup\u003e\u0026nbsp;\u003c/sup\u003e travel grants and lecture fees from Pfizer, Novartis, Eli Lilly, MSD, Roche, Gilead and AstraZeneca;\u0026nbsp;, Natalia Cichowska-Cwalińska\u003csup\u003e\u0026nbsp;\u003c/sup\u003etravel grants and lecture fees from Novartis, Renata Pacholczak-Madej\u0026nbsp;travel grants from Accord, BMS, MSD, lecture fees from AstraZeneca, BMS, MSD, GSK, Novartis, Roche, Anna G\u0026oacute;rniak\u003csup\u003e\u0026nbsp;\u003c/sup\u003etravel grants from Roche and Novartis, Joanna Pleskacz\u003csup\u003e\u0026nbsp;\u003c/sup\u003e travel grants from BMS, MSD, Amgen, Novartis; lecture fees from Novartis, Pierre Fabre,\u0026nbsp;Bogumiła Czartoryska-Arłukowicz:\u0026nbsp;travel grants and lecture fees from Eli Lilly, Novartis, Pfizer, Astra, Gilead, Roche,\u0026nbsp;Michał Jarząb\u003csup\u003e\u0026nbsp;\u003c/sup\u003econference fees by Gilead, Roche, speaker\u0026rsquo;s honoraria by Novartis, Roche, Lilly, Pfizer, Teva, Exact Sciences, Mammotome, advisory boards by Novartis, Pfizer;, Marek Jasi\u0026oacute;wka\u003csup\u003e\u0026nbsp;\u003c/sup\u003electure fees from GSK, \u0026nbsp;MSD, BMS, Roche and AstraZeneca;\u0026nbsp;Aleksandra Łacko\u003csup\u003e\u0026nbsp;\u003c/sup\u003ereports travel grants and lecture honoraria from Astra Zeneca, Pfizer, Novartis, Eli Lilly, Roche, Gilead Science including advisory board member role; Małgorzata Meluch:\u0026nbsp;lectures fees: Novartis, Astra Zeneca, Lilly, Pfizer, Roche, support for conference attendance: Lilly, \u003cem\u003einternational training programs: Lilly, Novartis, Pfizer\u003c/em\u003e\u003cem\u003e,\u0026nbsp;\u003c/em\u003eMirosława P\u0026uuml;sk\u0026uuml;ll\u0026uuml;oğlu\u003csup\u003e\u0026nbsp;\u003c/sup\u003ereceived travel grants and lecture honoraria from AstraZeneca, Roche, Novartis, Eli Lilly, Janssen, Gilead, and Amgen.\u0026nbsp;Katarzyna Świderska, Iwona Danielewicz, Ewa W\u0026oacute;jcik, Wioleta Łabul,\u003csup\u003e\u0026nbsp;\u003c/sup\u003eJakub Wronowicz\u003csup\u003e\u0026nbsp;\u003c/sup\u003ereport no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eSupplemental material\u003c/p\u003e\n\u003cp\u003eSupplemental material for this article is available online.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLiu C, Yang M, Zhang D, Chen M, Zhu D (2022) Clinical cancer immunotherapy: Current progress and prospects. Front Immunol. https://doi.org/10.3389/fimmu.2022.961805\u003c/li\u003e\n\u003cli\u003eSordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez-Rodriguez AP, Mart\u0026iacute;nez-P\u0026eacute;rez A, Rodrigo JP, Garc\u0026iacute;a-Pedrero JM, Gonzalez S (2023) Chemo-Immunotherapy: A New Trend in Cancer Treatment. Cancers (Basel). https://doi.org/10.3390/cancers15112912\u003c/li\u003e\n\u003cli\u003eMc Neil V, Lee SW (2025) Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies. Cancers (Basel). https://doi.org/10.3390/cancers17091408\u003c/li\u003e\n\u003cli\u003eLiu Y, Hu Y, Xue J, Li J, Yi J, Bu J, Zhang Z, Qiu P, Gu X (2023) Advances in immunotherapy for triple-negative breast cancer. Mol Cancer. https://doi.org/10.1186/s12943-023-01850-7\u003c/li\u003e\n\u003cli\u003eGeurts V, Kok M (2023) Immunotherapy for Metastatic Triple Negative Breast Cancer: Current Paradigm and Future Approaches. Curr Treat Options Oncol 24:628\u0026ndash;643\u003c/li\u003e\n\u003cli\u003eSriramulu S, Thoidingjam S, Speers C, Nyati S (2024) Present and Future of Immunotherapy for Triple-Negative Breast Cancer. Cancers (Basel). https://doi.org/10.3390/cancers16193250\u003c/li\u003e\n\u003cli\u003eLehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Journal of Clinical Investigation 121:2750\u0026ndash;2767\u003c/li\u003e\n\u003cli\u003eLehmann BD, Jovanović B, Chen X, Estrada M V., Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA (2016) Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One. https://doi.org/10.1371/journal.pone.0157368\u003c/li\u003e\n\u003cli\u003eGrinda T, Antoine A, Jacot W, et al (2023) Real-world clinical and survival outcomes of patients with early relapsed triple-negative breast cancer from the ESME national cohort. Eur J Cancer. https://doi.org/10.1016/j.ejca.2023.05.023\u003c/li\u003e\n\u003cli\u003eKesireddy M, Elsayed L, Shostrom VK, Agarwal P, Asif S, Yellala A, Krishnamurthy J (2024) Overall Survival and Prognostic Factors in Metastatic Triple-Negative Breast Cancer: A National Cancer Database Analysis. Cancers (Basel). https://doi.org/10.3390/cancers16101791\u003c/li\u003e\n\u003cli\u003eSchmid P, Adams S, Rugo HS, et al (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine 379:2108\u0026ndash;2121\u003c/li\u003e\n\u003cli\u003eEmens LA, Adams S, Barrios CH, et al (2021) First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Annals of Oncology 32:983\u0026ndash;993\u003c/li\u003e\n\u003cli\u003eMiles D, Gligorov J, Andr\u0026eacute; F, et al (2021) Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Annals of Oncology 32:994\u0026ndash;1004\u003c/li\u003e\n\u003cli\u003eCortes J, Rugo HS, Cescon DW, et al (2022) Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine 387:217\u0026ndash;226\u003c/li\u003e\n\u003cli\u003eCortes J, Cescon DW, Rugo HS, et al (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet 396:1817\u0026ndash;1828\u003c/li\u003e\n\u003cli\u003eCardoso F, Paluch-Shimon S, Schumacher-Wulf E, et al (2024) 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. https://doi.org/10.1016/J.BREAST.2024.103756\u003c/li\u003e\n\u003cli\u003eGennari A, Andr\u0026eacute; F, Barrios CH, et al (2021) ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Annals of Oncology 32:1475\u0026ndash;1495\u003c/li\u003e\n\u003cli\u003eQi Y, Yan X, Wang C, Cao H, Liu G (2022) Predictive value of PD-L1 expression to the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer: A systematic review and meta-analysis. Front Pharmacol. https://doi.org/10.3389/fphar.2022.1004821\u003c/li\u003e\n\u003cli\u003eVillacampa G, Tolosa P, Salvador F, S\u0026aacute;nchez-Bayona R, Villanueva L, Dienstmann R, Ciruelos E, Pascual T (2022) Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in first-line metastatic triple-negative breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. https://doi.org/10.1016/j.ctrv.2022.102352\u003c/li\u003e\n\u003cli\u003eWu Q, Wu C, Xie X (2023) Efficacy and Safety of Immune Checkpoint Inhibitors in Triple-negative Breast Cancer: A Study Based on 41 Cohorts Incorporating 6558 Participants. Journal of Immunotherapy 46:29\u0026ndash;42\u003c/li\u003e\n\u003cli\u003eYang J, Liu C, Guo Y, Guo W, Wu X (2024) Addition of PD-1/PD-L1 inhibitors to chemotherapy for triple-negative breast cancer: a meta-analysis. Front Oncol. https://doi.org/10.3389/fonc.2024.1309677\u003c/li\u003e\n\u003cli\u003eLiang X, Chen X, Li H, Li Y (2023) Immune checkpoint inhibitors in first-line therapies of metastatic or early triple-negative breast cancer: a systematic review and network meta-analysis. Front Endocrinol (Lausanne). https://doi.org/10.3389/fendo.2023.1137464\u003c/li\u003e\n\u003cli\u003eSkinner KE, Haiderali A, Huang M, Schwartzberg LS, Skinner KE (2021) Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer. Future Oncology 17:931\u0026ndash;941\u003c/li\u003e\n\u003cli\u003eZhang Z, Zhang Y, Liu C, et al (2023) A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer. Cancer Innovation 2:172\u0026ndash;180\u003c/li\u003e\n\u003cli\u003eQian X, Tao Y, Chen H, Li X, Wang Y, Xu X, Li S, Chen H, Cang S, Liu Y (2025) Real-world evaluation of the efficacy of immune checkpoint inhibitors in the treatment of metastatic breast cancer. Oncol Lett. https://doi.org/10.3892/ol.2024.14775\u003c/li\u003e\n\u003cli\u003eNotice of the Minister of Health of the Republic of Poland, dated 20 June 2023, concerning the list of reimbursed medicinal products, foods for special medical purposes, and medical devices, effective as of 1 July 2023. In: Internet. https://www.gov.pl/web/zdrowie/obwieszczenie-ministra-zdrowia-z-dnia-20-czerwca-2023-r-w-sprawie-wykazu-lekow-refundowanych-srodkow-spozywczych-specjalnego-przeznaczenia-zywieniowego-oraz-wyrobow-medycznych-na-1-lipca-2023-r?utm_source=chatgpt.com. Accessed 26 Jul 2025\u003c/li\u003e\n\u003cli\u003eCortes J, Cescon DW, Rugo HS, et al (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet 396:1817\u0026ndash;1828\u003c/li\u003e\n\u003cli\u003eEisenhauer EA, Therasse P, Bogaerts J, et al (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228\u0026ndash;247\u003c/li\u003e\n\u003cli\u003ePembrolizumab - Summary of Product Characteristics. In: Internet. https://www.ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf. Accessed 26 Jul 2025\u003c/li\u003e\n\u003cli\u003eCancer Institute N (2017) Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. \u003c/li\u003e\n\u003cli\u003eLoibl S, Andr\u0026eacute; F, Bachelot T, et al (2023) Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up\u0026dagger;. Annals of Oncology. https://doi.org/10.1016/j.annonc.2023.11.016\u003c/li\u003e\n\u003cli\u003eVoorwerk L, Slagter M, Horlings HM, et al (2019) Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med 25:920\u0026ndash;928\u003c/li\u003e\n\u003cli\u003eTolaney SM, de Azambuja E, Kalinsky K, et al (2025) Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1\u0026ndash;positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2025.43.17_SUPPL.LBA109\u003c/li\u003e\n\u003cli\u003eBidard F-C, Mayer EL, Park YH, et al (2025) First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. New England Journal of Medicine. https://doi.org/10.1056/NEJMOA2502929\u003c/li\u003e\n\u003cli\u003eThompson JC, Scholes DG, Carpenter EL, Aggarwal C (2023) Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors. British Journal of Cancer 2023 129:12 129:1893\u0026ndash;1902\u003c/li\u003e\n\u003cli\u003eKubeczko M, Polakiewicz-Gilowska A, D\u0026rsquo;Amico A, Chrabański O, Świderska K, Chmielik E, Blamek S, Handkiewicz-Junak D, Jarząb M (2024) The role of FDG PET assessment in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 inhibitors in the second-line setting. Front Oncol. https://doi.org/10.3389/FONC.2024.1454844\u003c/li\u003e\n\u003cli\u003eFilippi L, Urso L, Ferrari C, Guglielmo P, Evangelista L (2024) The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective. Eur J Nucl Med Mol Imaging 52:263\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pembrolizumab, metastatic triple negative breast cancer, real world data, first line treatment, progression-free survival, safety","lastPublishedDoi":"10.21203/rs.3.rs-7367639/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7367639/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePembrolizumab combined with chemotherapy has improved clinical outcomes in PD-L1-positive metastatic triple-negative breast cancer (mTNBC) in KEYNOTE-355 trial. However, real-world studies confirming these data are lacking. We aimed to evaluate the efficacy and safety of pembrolizumab with chemotherapy in a real-world cohort of Polish patients with PD-L1-positive (CPS\u0026thinsp;\u0026ge;\u0026thinsp;10), previously untreated mTNBC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective study included 89 female patients, who initiated this regimen between September 2022 and February 2025 at thirteen Polish oncology centers. Patients received pembrolizumab combined with paclitaxel or carboplatin/gemcitabine as per Polish reimbursement criteria. Primary endpoints included overall survival (OS), progression-free survival (PFS), and safety, assessing immune-related adverse events (irAEs) and chemotherapy-related toxicities (trAEs) according to CTCAE v5.0 criteria.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe median follow-up was 10.1 months (IQR 5.5\u0026ndash;14.8). OS data were immature (n\u0026thinsp;=\u0026thinsp;15 events). Median PFS was 9.3 months (95% CI: 6.6\u0026ndash;14.7). A higher number of metastatic sites was significantly associated with shorter PFS (HR\u0026thinsp;=\u0026thinsp;1.43, 95% CI: 1.09\u0026ndash;1.88, p\u0026thinsp;=\u0026thinsp;0.01), while other clinical and treatment parameters showed no significant associations. irAEs occurred in 37.1% (n\u0026thinsp;=\u0026thinsp;33) of patients, one-third were grade 3/4. Neither irAE occurrence (p\u0026thinsp;=\u0026thinsp;0.55) nor corticosteroid use (p\u0026thinsp;=\u0026thinsp;0.67) significantly impacted PFS.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this real-world cohort of first-line pembrolizumab plus chemotherapy for PD-L1-positive mTNBC, treatment achieved meaningful efficacy and an acceptable safety profile, with median PFS broadly consistent with clinical trial results. OS data remain immature. Clinical parameters showed limited prognostic value, suggesting a need for integrating molecular biomarkers and tumor biology into treatment selection and prognostication to optimize patient outcomes.\u003c/p\u003e","manuscriptTitle":"First real-world experience with 1L pembrolizumab and chemotherapy treatment for advanced triple-negative breast cancer in Poland: safety analysis and first survival outcomes from a multicenter cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-23 11:05:47","doi":"10.21203/rs.3.rs-7367639/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ab1e7ace-e667-4743-b4b3-bf21218895d9","owner":[],"postedDate":"September 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T08:27:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-23 11:05:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7367639","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7367639","identity":"rs-7367639","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}