Clinical efficacy and safety of Cadonilimab in the treatment of advanced gynecological malignancies: a retrospective, real-world study

Clinical efficacy and safety of Cadonilimab in the treatment of advanced gynecological malignancies: a retrospective, real-world study | 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 Clinical efficacy and safety of Cadonilimab in the treatment of advanced gynecological malignancies: a retrospective, real-world study Yisidan Huang, Yuting Zeng, Cui Zhang, Can Yang, Hanqun Zhang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6233481/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Aug, 2025 Read the published version in BMC Cancer → Version 1 posted 11 You are reading this latest preprint version Abstract Background Cadonilimab, recognized as the most rapidly developed Chinese drug in the field of cervical cancer, received marketing approval in China in 2022. We conducted a study to investigate the safety and efficacy of Cadonilimab, combined with and without chemotherapy or bevacizumab treatment, in patients with recurrent / metastatic gynecological malignancies. Methods We retrospectively enrolled 60 patients with recurrent / metastatic gynecological malignant tumors, confirmed by pathology or cytology from July 2022 to December 2024. All patients received at least two cycles of Cadonilimab. The primary endpoints were the investigator-confirmed objective response rate and disease control rate according to RECIST v1.1. Secondary endpoints included progression-free survival and safety. Results 56 patients were included in the efficacy analysis. In the study population, there were 16 first-line patients with advanced cervical cancer, ORR was 81.3%(13/16,95% CI,57 to 93.4),DCR was 93.8%(15/16,95% CI 71.7 to 98.9); There were 30 second-line patients, ORR was 36.7%༈11/30,95% CI,21.9 to 54.5༉,DCR was 90%(27/30,95% CI 74.4 to 96.5)。A total of 41 patients (73.2%) reported at least one treatment-related adverse event, with the most common being anemia (71.4%), nausea (28.6%), and myelosuppression (25%). 9 patients (16.1%) experienced G3-4 TRAEs. Additionally, 11 patients (19.6%) developed immune-related adverse events of G1-2. Importantly, no treatment-related deaths occurred during the study. Conclusion Cadonilimab with or without chemotherapy/bevacizumab had a promising antitumor activity and manageable safety profile in the treatment of recurrent/metastatic gynecological malignancies. Cadonilimab Gynecological malignancies Immunotherapy Safety Figures Figure 1 Figure 2 INTRODUCTION According to the 2022 Global Burden of Cancer Data Report released by the World Health Organization's International Agency for Research on Cancer (IARC), there are projected to be 19.96 million new cases of cancer and 9.74 million cancer-related deaths worldwide in 2022. Approximately one in five individuals, regardless of gender, will develop cancer in their lifetime, while about one in nine men and one in twelve women will succumb to the disease [1] . In China, women face significant threats from various cancers, including lung cancer, breast cancer, thyroid cancer, and gynecological malignant tumors [2] . The three most prevalent gynecological malignant tumors are cervical cancer, endometrial cancer, and ovarian cancer, with trophoblastic malignant tumors and other reproductive tract malignant tumors also being notable [3] . In 2022, there were an estimated 1.57 million new cases of cervical cancer in the country, resulting in approximately 55,700 deaths. Additionally, the number of endometrial cancer cases in 2022 was around 77,000, with about 13,500 deaths [4] . Furthermore, there were 52,100 new cases of ovarian cancer reported in the Chinese population, leading to 22,500 deaths [5] . Currently, the primary treatments for gynecological tumors include surgery, chemotherapy, radiotherapy, and targeted therapy. Despite these interventions, patients continue to experience high rates of recurrence and metastasis, leading to poor prognoses, low survival rates, and shortened survival periods. Specifically, the survival rate for patients with recurrent and metastatic cervical cancer is only 17% [6] , while the 5-year survival rate for those with recurrent or metastatic endometrial cancer is approximately 15% [7] . In the case of ovarian cancer, most patients are diagnosed at an advanced stage. Overall, the 5-year survival rate for cancer patients is around 40% [8] . For patients who have undergone systematic surgical treatment and chemotherapy, the 5-year survival rate for those with advanced stage cancer falls below 30% [9] . With the continuous and in-depth development of immune checkpoint inhibitors (ICIs) in tumor treatment, immunotherapy has emerged as a prominent approach among various anti-tumor therapies. As early as 2013, immunotherapy was recognized as the leading scientific breakthrough of the year by Science magazine [10] . In the realm of gynecological oncology, the primary immunotherapy methods currently employed include immune checkpoint inhibitors (ICIs), adoptive cellular immunotherapy (ACT), therapeutic vaccines, and cytokine therapy. Notably, immune checkpoint inhibitors (ICIs) are relatively advanced, supported by substantial clinical experience and validated through numerous clinical trials. Immune checkpoint inhibitors (ICIs) primarily restore the patient's immune system's capacity to attack cancer cells by blocking or inhibiting immune checkpoint molecules present on the surface of tumor cells. In the human body, immune checkpoint molecules function as negative regulatory entities that suppress the activity of immune cells, thereby enabling tumor cells to evade immune system detection. The role of ICIs is to obstruct these negative regulatory molecules, allowing immune cells to regain their ability to target and eliminate tumor cells. Based on their specific targets, ICIs can be categorized into three major classes of monoclonal antibodies: cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, programmed death factor 1 (PD-1) monoclonal antibodies, and programmed death factor ligand 1 (PD-L1) monoclonal antibodies. In the field of gynecological oncology, the results of the Keynote-A18 trial demonstrated that the addition of pembrolizumab increased the 2-year progression-free survival (PFS) rate of patients from 57.3–67.8%, and the 3-year PFS rate improved from 56.9–69.3%. An update on overall survival (OS) data indicated that the 3-year OS rate rose from 74.8–82.6% [11] . The Keynote-B21 trial revealed that in high-risk postoperative patients with endometrial cancer, pembrolizumab in combination with adjuvant therapy significantly enhances disease-free survival (DFS) in the deficient mismatch repair (DMMR) population [12] . Additionally, the Atalante study illustrated that atezolizumab, when combined with platinum-based chemotherapy and bevacizumab, can elevate the 5-year survival rate of patients with platinum-sensitive recurrent epithelial ovarian cancer from 17–27% [13] . As research progresses, immune checkpoint inhibitors (ICIs) are expected to play an increasingly vital role in the immunotherapy of various gynecological tumors. Cadonilimab is a novel PD-1/CTLA-4 bispecific antibody tumor immunotherapy drug independently developed by China Kangfang Biologics. It received marketing approval from the National Medical Products Administration of China on June 29, 2022, primarily for the treatment of patients with recurrent or metastatic cervical cancer (R/MCC) who have failed previous platinum-containing chemotherapy. Cadonilimab exhibits high affinity and operates by effectively blocking the PD-1 and CTLA-4 pathways, which in turn enhances the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ) [14] . This mechanism activates T cells to counteract immunosuppressive responses, promotes tumor-specific T cell immune activation, and ultimately inhibits tumor growth. Cadonilimab is currently being investigated not only in the field of cervical cancer but also in various studies involving other malignant tumors, including lung cancer, gastric cancer, and liver cancer. The results of the COMPASSION-03 trial indicated that during the phase 1b dose escalation phase, no dose-limiting toxicities were observed, suggesting that the overall safety profile of Cadonilimab is favorable. In the phase 2 clinical trial, Cadonilimab demonstrated significant anti-tumor activity and long-term survival benefits. Specifically, it exhibited a high overall response rate (ORR) in patients with cervical cancer. The median follow-up time for the cervical cancer cohort was 14.6 months, as assessed by the Independent Imaging Review Committee (IRRC). This committee evaluated the ORR of Cadonilimab monotherapy in patients with advanced cervical cancer who had previously failed platinum-containing chemotherapy. The ORR was found to be 32.3%, comprising a complete response (CR) of 14.1% (14 cases) and a partial response (PR) of 18.2% (18 cases) [15] . Additionally, Cadonilimab demonstrated manageable safety and robust anti-tumor activity in the treatment of advanced solid tumors. Consequently, we aim to further investigate the effectiveness and safety of Cadonilimab in treating gynecological cancer patients in real-world settings. PATIENTS AND METHODS Patients In this study, we retrospectively included patients with pathologically or cytologically confirmed diagnoses who received cadonilimab as second-line or later-line therapy from July 2022 to December 2024. The patient cohort comprised individuals with recurrent or metastatic gynecological malignancies. Inclusion criteria were as follows: pathologically or cytologically confirmed recurrent or metastatic gynecological malignancy, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, at least one measurable lesion, and a minimum of one cycle of cadonilimab. Exclusion criteria included: high bleeding risk, severe autoimmune disease, grade III hypertension, cardiac insufficiency, gastrointestinal dysfunction, intestinal obstruction, failure to follow up, incomplete clinical data, and the absence of measurable lesions. A total of 60 patients' clinical data were collected, summarizing demographic and clinical characteristics such as age, gender, diagnosis, stage, pathological subtype, presence of liver or brain metastasis, ECOG PS, previous treatment lines and regimens, laboratory and radiological data, as well as adverse events (AEs). The study was approved by the Ethics Committee of the Guizhou Provincial People’s Hospital. Informed consent was waived due to the retrospective nature of this study. Cadonilimab is administered via intravenous infusion at a recommended dose of 6 mg/kg every two weeks, continuing until either disease progression or intolerable toxicity occurs. The initial dosage is determined by the oncologist based on the patient's condition and may be adjusted in response to any intolerable side effects. The combination regimen is prescribed in accordance with the guidelines established by the National Comprehensive Cancer Network or the Chinese Society of Clinical Oncology. Assessments According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, computerized pelvic magnetic resonance imaging was utilized to assess the patient's lesions at baseline. During the treatment period, the patient's efficacy was evaluated biweekly, with assessments conducted by the attending physician in accordance with RECIST 1.1. This version categorizes efficacy indicators into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The overall response rate (ORR) was calculated as the ratio of CR plus PR, while the disease control rate (DCR) was determined as the ratio of CR plus PR plus SD. Clinical benefit was defined as patients achieving CR, PR, or SD as their best response, whereas nonclinical benefit was characterized by patients experiencing PD as their best response. Adverse events were recorded from the first day of treatment through one month after treatment completion and were graded according to the National Cancer Institute's Adverse Event Evaluation Criteria, version 5.0. End Points The primary endpoints are Objective Response Rate (ORR) and Disease Control Rate (DCR). ORR is defined as the proportion of patients whose tumor volume decreases to a predetermined value after treatment and who can maintain this minimum for the specified duration according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This includes both complete response (CR) and partial response (PR) and is expressed as the sum of these proportions. DCR, also based on RECIST 1.1, refers to the percentage of cases that achieve either a response (PR + CR) or stable disease (SD) after treatment, relative to the total number of evaluable cases. Secondary endpoints include progression-free survival (PFS), which is the time from the first dose to disease progression (PD) or death from any cause. Statistical Analysis Statistical analyses were conducted using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous data are presented as means with 95% confidence intervals (CIs), while categorical data are reported as frequencies or percentages (%). RESULTS A total of 60 patients were screened between July 2022 and December 2024, including 46 patients (76.7%) with cervical cancer, 8 cases of endometrial cancer (13.3%), 1 case of endometrial adenosarcoma (1.7%), 1 case of vaginal melanoma (1.7%), 1 case of vulvar cancer (1.7%), 1 case of choriocarcinoma (1.7%)and 2 case of ovarian cancer (3.3%). 54 patients (90.0%)were in menopausal state, 32 patients(53.3%) had previous surgery, 11 patients (18.3%) had previously received chemotherapy, 23 patients(38.3%) had previously received concurrent chemoradiotherapy, 2 patient(3.3%) had previously received chemotherapy plus Targeted therapy and 3 patients (5%)had previously received radiotherapy. 15 patients (25%)had only local recurrence, and 8 patients(13.3%) had recurrence and distant metastasis. (Table 1). According to the patients' use of Cadonilimab, 4 patients were excluded because they had only used Cadonilimab for one cycle and did not return to the hospital to continue treatment, making it impossible to evaluate the patient's efficacy. As of the data cutoff, 18 (32.1%) patients were still receiving treatment, and 38 (67.9%) patients had stopped treatment, of which 7 (12.5%) patients stopped due to PD and 1(2.3%) patient stopped taking medication due to hypothyroidism. Efficacy Measures In the Efficacy-Evaluable Population, 2 patients (3.3%) achieved a complete response (CR), 24 patients (40.0%) achieved a partial response (PR), 26 patients (43.3%) developed stable disease (SD), 4 patients (6.7%) developed progressive disease (PD) (Fig. 1 ). This patient had received only one cycle of Cadonilimab treatment, and due to not returning to the hospital for further treatment and efficacy evaluation, the patient's efficacy could not be assessed. Among the responding patients, the overall response rate (ORR) was 43.3% (95% CI, 31.6 to 55.9, and the disease control rate (DCR) was 86.7% (95% CI, 75.8 to 93.1; Table 2). In the study population, there were 16 first-line patients with advanced cervical cancer, ORR was 81.3%(13/16,95% CI,57 to 93.4),DCR was 93.8%(15/16,95% CI 71.7 to 98.9); There were 30 second-line patients, ORR was 36.7%༈11/30,95% CI,21.9 to 54.5༉,DCR was 90%(27/30,95% CI 74.4 to 96.5; Table 3). Median PFS was not reached(Fig. 2 ). Safety In the responder population, 41 (73.2%) patients experienced at least one treatment-related adverse event (TRAE), the most common of which were anemia (71.4%), nausea (28.6%), and myelosuppression (25%) (Table 4). 9 (16.1%) patients experienced Grade 3–4 TRAEs, including 5 (8.9%) due to anemia and 4 (7.1%) due to myelosuppression. 9 (16.0%) patients experienced vomiting, 2 patients (4.7%) experienced cardiotoxic reactions. The electrocardiogram and cardiac enzyme results of these 2 patients were mildly abnormal. No treatment-related deaths occurred during treatment. Immune-related adverse reactions occurred in 11 (19.6%) patients, including 1 (1.7%) patient who developed immune osteitis and myositis, and 1 (1.7%) patient who developed immune myocarditis. 8 (14.3%) patients experienced infusion-related adverse reactions, of which 1 (1.7%) patient showed mild palpitations, chest tightness, and shortness of breath after infusion of Cadonilimab, which resolved spontaneously after rest; 3 (7.0%) patients After the infusion of Cadonilimab, not only palpitations, chest tightness, and shortness of breath occurred, but also systemic itching, rashes, etc. The patient's discomfort was relieved after anti-allergic treatment; 2 (3.6%) patients suffered from Cadonilimab infusion. After taking the monoclonal antibody, the patient developed chills and high fever, but the patient's condition improved after treatment. DISCUSSION The GOG-240 study [16] demonstrated that patients receiving comprehensive treatment that included anti-angiogenic drugs experienced improved overall survival, with a median overall survival extension of 3.5 months, compared to those treated with chemotherapy alone. This finding establishes the basis for standard chemotherapy in combination with bevacizumab. Additionally, Lizumab is recognized as the standard first-line treatment for recurrent or metastatic cervical cancer (r/m CC). The KEYNOTE-826 study [17] investigated the efficacy of incorporating pembrolizumab, with or without bevacizumab, into chemotherapy regimens. The findings demonstrated that the addition of the PD-1 inhibitor pembrolizumab extends the first-line treatment duration for patients with cervical cancer, resulting in a median overall survival (OS) of 26.4 months. The subsequent phase III BEATcc study [18] demonstrated that, when chemotherapy and bevacizumab were combined with atezolizumab, the median progression-free survival (mPFS) for patients increased from 10.4 months to 13.7 months, while the median overall survival (mOS) improved from 22.8 months to 32.1 months. The OS of patients with advanced first-line cervical cancer is approaching 3 years. These studies are gradually improving survival times for advanced cervical cancer. The current first-line treatment options for recurrent/metastatic cervical cancer are carboplatin, paclitaxel, and bevacizumab, but the survival rate of this treatment option is still limited [19] . The recently announced COMPASSION-16 study [20] is a randomized, placebo-controlled, multi-center, double-blind phase III clinical trial. The results of the study showed that the median PFS of the Cadonilimab group and the placebo group were 13.3 months and 8.2 months, respectively. Months, the risk of disease progression or death was reduced by 38%. The current median OS has not been reached, but there is a significant benefit trend, and the study also included 28% of patients with negative PD-L1 expression (CPS < 1). The KEYNOTE-826 study [17] shows that immunotherapy can significantly benefit patients with positive PD-L1 expression (CPS ≥ 1), but the benefit is not significant for patients with negative PD-L1 expression (CPS < 1). Therefore, current guidelines recommend pembrolizumab. The application population of anti-PD-L1 is mainly limited to patients with positive PD-L1 expression. The COMPASSION-16 study showed that for patients with negative PD-L1 expression (CPS < 1), the median progression-free survival reached 12 months (vs 8.2m), and the risk of disease progression or death was reduced by 27% (HR 0.73); For patients with positive PD-L1 expression (CPS ≥ 1), the median progression-free survival reached 13.5 months (vs 8.3m), and the risk of disease progression or death was reduced by 38% (HR 0.62). Regardless of PD-L1 expression status, all patients can benefit from Cadonilimab combination therapy. And because in clinical practice many patients have contraindications to the use of bevacizumab or are not suitable for bevacizumab, in the subgroup analysis of COMPASSION-16, for patients who are not suitable for bevacizumab, The OS of previous chemotherapy and chemotherapy + pembrolizumab did not reach 2 years, while the OS of chemotherapy + Cadonilimab was as high as 28.2 months. Cadonilimab has achieved real benefits for the entire population to a certain extent. Since 2022, Cadonilimab has shown good efficacy and safety in various malignant tumors such as liver cancer [21] , lung cancer [22] , and nasopharyngeal cancer [23] . Many dual-immunity combination studies, such as Checkmate-227 [24, 25] , have suggested that PD-1 combined with CTLA-4 can bring better survival benefits to people with negative PD-L1 expressions. In comparison to the combination therapy of anti-PD-1 monoclonal antibodies and anti-CTLA-4 monoclonal antibodies [14] , Cadonilimab exhibits significantly lower toxicity and demonstrates clear advantages in both safety and efficacy. Cadonilimab was designed with an Fc empty backbone to eliminate Fc-mediated effector functions, thereby reducing the production of pro-inflammatory cytokines such as IL-6 and IL-8. Elevated IL-6 levels in patients undergoing anti-PD-1 therapy play a critical role in immune-related adverse events (irAE), and increased IL-6 is associated with poor clinical responses to PD-1 blockade therapy. Additionally, high levels of IL-8 are linked to reduced efficacy of immune checkpoint inhibitor therapy. One study [14] found that Cadonilimab resulted in the lowest secretion of IL-6 and IL-8 compared to nivolumab and ipilimumab. This characteristic may represent a distinct mechanism of action for Cadonilimab differing from the combination of anti-PD-1 and anti-CTLA-4 antibodies, which may influence both safety and efficacy. In this study, Cadonilimab combination therapy demonstrated good therapeutic effect and controllable safety in the population with advanced gynecological malignancies. Among the population with evaluable efficacy, the ORR was 46.4% (95% CI, 34 to 59.3) and DCR 92.9% (95% CI, 83 to 97.2). In addition, there were 46 patients with advanced cervical cancer in this study, 16 of whom were treated with Cadonilimab combined with chemotherapy ± bevacizumab as the first-line regimen, with an ORR of 81.3% (95% CI, 57 to 93.4 ), with a DCR of 93.8% (95% CI, 71.7 to 98.9). The AK104-210 trial [15] is a prospective, multi-cohort phase II clinical trial designed to evaluate the efficacy of different doses of Cadonilimab combined with platinum-based chemotherapy with or without bevacizumab in the first-line treatment of recurrent or metastatic cervical cancer. Efficacy and safety, the ORR of the three cohorts in the study were 66.7%, 68.8% and 92.3% respectively; among them, Cadonilimab (10mg Q3W) + chemotherapy ± bevacizumab (A10 + B10 cohort), the overall ORR in the entire population was 79.3%, which was higher than the entire population of pembrolizumab + chemotherapy ± bevacizumab in the keynote-826 trial ORR 65.9%. The COMPASSION-16 study [20] is a randomized, double-blind, multi-center, placebo-controlled trial in patients aged 18–75 years with untreated refractory, recurrent or metastatic cervical cancer, according to 1: 1 ratio random distribution The patients were enrolled in the Cadonilimab group (10 mg/kg once) or the placebo group. Both groups received platinum-containing chemotherapy, with or without bevacizumab, once every 3 weeks for a total of 6 cycles; then Maintenance treatment is given every 3 weeks for up to 2 years. In this study, the Cadonilimab group had a high tumor response rate, with an ORR of 82.9% and a DCR of 94% in the ITT population. In this study, the Cadonilimab combination treatment regimen was effective in patients with advanced first-line cervical cancer. The ORR and DCR are similar to the data of the first two studies, proving the high efficiency and high tumor response rate of Cadonilimab combined with chemotherapy ± bevacizumab in the first-line treatment of advanced cervical cancer. In this study, 30 people used Cadonilimab combined with chemotherapy ± bevacizumab as the second-line regimen. The ORR was 36.7% (95% CI, 21.9 to 54.5), and the DCR was 90% (87%). CI,74.4 to 96.5). AK104-201 [15] is a single-arm, phase II clinical trial designed to evaluate the efficacy and safety of Cadonilimab monotherapy in the second-line treatment of recurrent or metastatic cervical cancer. The results of this study showed that in 100 patients with evaluable efficacy Among patients, the objective response rate (ORR) of Cadonilimab in the entire population was 33%. The ORR of Cadonilimab combination therapy in the second-line treatment of neck cancer is 36.7%, slightly higher than the AK104-201 study, and much higher than Keynote-158 [26] , which has a similar sample size, the same number of lines of population, and a similar treatment plan as AK104-201. In the trial, the ORR of pembrolizumab in the entire population was 14.3%. In terms of safety, the treatment-related adverse events of Cadonilimab were grade 2 and below. 41 patients (73.2%) experienced at least one treatment-related adverse event (TRAE), and the incidence of greater than grade 3 was only 16.1%, which is slightly lower than the incidence of treatment-related adverse reactions used in studies of patients with advanced cervical cancer [27] . The most reported adverse events were anemia (71.4%), nausea (28.6%), and bone marrow suppression (25%). Nine patients (16.1%) experienced treatment-related adverse events (TRAEs) of grade G3-4 or higher. Following symptomatic and supportive treatment, such as blood transfusions and leukocyte elevation, the adverse reactions were significantly alleviated. Additionally, 11 patients (19.6%) developed immune-related adverse reactions of grade G1-2. This study has several limitations. First, within the collected population of gynecological malignant tumor patients, cervical cancer patients constitute the largest group, followed by those with endometrial cancer. In contrast, other cancer types, such as ovarian cancer and vaginal melanoma, each had only one case represented. This disparity limits our ability to fully assess the effectiveness and safety of Cadonilimab in treating a diverse range of gynecological tumors. Secondly, because this study is a retrospective study, the patients' genetic information and biomarkers such as PD-L1 were not collected for in-depth exploration. We will further improve this aspect in the future. 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A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study) [J]. Lung Cancer, 2023, 184: 107355. [23] CHEN Q Y, GUO S S, LUO Y, et al. Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study [J]. Oral Oncol, 2024, 151: 106723. [24] O'BYRNE K J, LEE K H, KIM S W, et al. First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients [J]. ESMO Open, 2022, 7(1): 100394. [25] PAZ-ARES L, CIULEANU T E, COBO M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [J]. Lancet Oncol, 2021, 22(2): 198–211. [26] MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study [J]. J Clin Oncol, 2020, 38(1): 1–10. [27] WU X, JI J, LOU H, et al. Efficacy and safety of cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, in previously treated recurrent or metastatic (R/M) cervical cancer: a multicenter, open-label, single-arm, phase II trial (075) [J]. Gynecologic Oncology, 2022, 166: S47-S8. Abbreviations ORR objective response rate DCR disease control rate PFS progression-free survival CR complete response PR partial response SD stable disease PD progressive disease CI confidence intervals IARC International Agency for Research on Cancer ICIs immune checkpoint inhibitors ACT adoptive cellular immunotherapy CTLA-4 cytotoxic T lymphocyte antigen 4 PD-1 programmed death factor 1 PD-L1 programmed death factor ligand 1 PFS progression-free survival OS overall survival DFS disease-free survival DMMR deficient mismatch repair R/MCC recurrent or metastatic cervical cancer IL-2 interleukin-2 IFN-γ interferon-γ IRRC Independent Imaging Review Committee ECOG PS Eastern Cooperative Oncology Group performance status AEs adverse events RECIST Response Evaluation Criteria in Solid Tumors mPFS median progression-free survival mOS median overall survival Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests The authors declare that they have no competing interests Authors' contributions All authors contributed to this study. H. conceived and designed the experiments, analyzed and interpreted the data, and contributed to writing the manuscript. Z.conducted , Z. analyzed research results, Y.Z.and assisted in manuscript preparation and editing. L.L.L.B.L. contributed to data acquisition and analysis, reviewed literature, provided intellectual input, and approved the final version of the manuscript. L. provided logistical and administrative support, ensured compliance with ethical standards, and reviewed and approved the manuscript for submission. Ethics approval and consent to participate The study was approved by the Ethics Committee of the Guizhou Provincial People’s Hospital. Informed consent was waived due to the retrospective nature of this study. Availability of data and materials The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Acknowledgements Not applicable Consent for publication Not applicable. References BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2024, 74(3): 229-63. HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022 [J]. J Natl Cancer Cent, 2024, 4(1): 47-53. YETKIN-ARIK B, KASTELEIN A W, KLAASSEN I, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy [J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188446. ZHENG R S, CHEN R, HAN B F, et al. [Cancer incidence and mortality in China, 2022] [J]. Zhonghua Zhong Liu Za Zhi, 2024, 46(3): 221-31. CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115-32. MARRET G, BORCOMAN E, LE TOURNEAU C. Pembrolizumab for the treatment of cervical cancer [J]. Expert Opin Biol Ther, 2019, 19(9): 871-7. BESTVINA C M, FLEMING G F. Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings [J]. Oncologist, 2016, 21(10): 1250-9. JIANG X, TANG H, CHEN T. Epidemiology of gynecologic cancers in China [J]. J Gynecol Oncol, 2018, 29(1): e7. JAYSON G C, KOHN E C, KITCHENER H C, et al. Ovarian cancer [J]. The Lancet, 2014, 384(9951): 1376-88. MCNUTT M. Cancer Immunotherapy [J]. Science, 2013, 342(6165): 1417-. LORUSSO D, XIANG Y, HASEGAWA K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial [J]. Lancet, 2024, 403(10434): 1341-50. VAN GORP T, CIBULA D, LV W, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer [J]. Ann Oncol, 2024. KURTZ J E, PUJADE-LAURAINE E, OAKNIN A, et al. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial [J]. J Clin Oncol, 2023, 41(30): 4768-78. PANG X, HUANG Z, ZHONG T, et al. Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity [J]. MAbs, 2023, 15(1): 2180794. GAO X, XU N, LI Z, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial [J]. Lancet Oncol, 2023, 24(10): 1134-46. TEWARI K S, SILL M W, PENSON R T, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240) [J]. Lancet, 2017, 390(10103): 1654-63. COLOMBO N, DUBOT C, LORUSSO D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer [J]. N Engl J Med, 2021, 385(20): 1856-67. OAKNIN A, GLADIEFF L, MARTíNEZ-GARCíA J, et al. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial [J]. Lancet, 2024, 403(10421): 31-43. COHEN P A, JHINGRAN A, OAKNIN A, et al. Cervical cancer [J]. The Lancet, 2019, 393(10167): 169-82. WU X, SUN Y, YANG H, et al. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China [J]. Lancet, 2024, 404(10463): 1668-76. YUAN G, CHEN Y, ZHU P, et al. Cadonilimab (PD-1/CTLA-4) in combination with lenvatinib in unresectable hepatocellular carcinoma (uHCC): A retrospective real-world study [J]. Heliyon, 2024, 10(19): e37616. ZHAO Y, MA Y, FAN Y, et al. A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study) [J]. Lung Cancer, 2023, 184: 107355. CHEN Q Y, GUO S S, LUO Y, et al. Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study [J]. Oral Oncol, 2024, 151: 106723. O'BYRNE K J, LEE K H, KIM S W, et al. First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients [J]. ESMO Open, 2022, 7(1): 100394. PAZ-ARES L, CIULEANU T E, COBO M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [J]. Lancet Oncol, 2021, 22(2): 198-211. MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study [J]. J Clin Oncol, 2020, 38(1): 1-10. WU X, JI J, LOU H, et al. Efficacy and safety of cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, in previously treated recurrent or metastatic (R/M) cervical cancer: a multicenter, open-label, single-arm, phase II trial (075) [J]. Gynecologic Oncology, 2022, 166: S47-S8. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table14.docx Cite Share Download PDF Status: Published Journal Publication published 19 Aug, 2025 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 14 Apr, 2025 Reviews received at journal 11 Apr, 2025 Reviewers agreed at journal 09 Apr, 2025 Reviews received at journal 07 Apr, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers invited by journal 04 Apr, 2025 Editor assigned by journal 03 Apr, 2025 Editor invited by journal 03 Apr, 2025 Submission checks completed at journal 03 Apr, 2025 First submitted to journal 03 Apr, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6233481","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":439049327,"identity":"d75bdb61-6238-4ecf-a407-5ca707108582","order_by":0,"name":"Yisidan Huang","email":"","orcid":"","institution":"Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yisidan","middleName":"","lastName":"Huang","suffix":""},{"id":439049328,"identity":"8bbe359f-eed2-458d-adef-2c402f775967","order_by":1,"name":"Yuting Zeng","email":"","orcid":"","institution":"Guizhou Provincial People’s 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to the 2022 Global Burden of Cancer Data Report released by the World Health Organization's International Agency for Research on Cancer (IARC), there are projected to be 19.96\u0026nbsp;million new cases of cancer and 9.74\u0026nbsp;million cancer-related deaths worldwide in 2022. Approximately one in five individuals, regardless of gender, will develop cancer in their lifetime, while about one in nine men and one in twelve women will succumb to the disease\u003csup\u003e[1]\u003c/sup\u003e. In China, women face significant threats from various cancers, including lung cancer, breast cancer, thyroid cancer, and gynecological malignant tumors\u003csup\u003e[2]\u003c/sup\u003e. The three most prevalent gynecological malignant tumors are cervical cancer, endometrial cancer, and ovarian cancer, with trophoblastic malignant tumors and other reproductive tract malignant tumors also being notable\u003csup\u003e[3]\u003c/sup\u003e. In 2022, there were an estimated 1.57\u0026nbsp;million new cases of cervical cancer in the country, resulting in approximately 55,700 deaths. Additionally, the number of endometrial cancer cases in 2022 was around 77,000, with about 13,500 deaths\u003csup\u003e[4]\u003c/sup\u003e. Furthermore, there were 52,100 new cases of ovarian cancer reported in the Chinese population, leading to 22,500 deaths\u003csup\u003e[5]\u003c/sup\u003e. Currently, the primary treatments for gynecological tumors include surgery, chemotherapy, radiotherapy, and targeted therapy. Despite these interventions, patients continue to experience high rates of recurrence and metastasis, leading to poor prognoses, low survival rates, and shortened survival periods. Specifically, the survival rate for patients with recurrent and metastatic cervical cancer is only 17%\u003csup\u003e[6]\u003c/sup\u003e, while the 5-year survival rate for those with recurrent or metastatic endometrial cancer is approximately 15%\u003csup\u003e[7]\u003c/sup\u003e. In the case of ovarian cancer, most patients are diagnosed at an advanced stage. Overall, the 5-year survival rate for cancer patients is around 40%\u003csup\u003e[8]\u003c/sup\u003e. For patients who have undergone systematic surgical treatment and chemotherapy, the 5-year survival rate for those with advanced stage cancer falls below 30%\u003csup\u003e[9]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWith the continuous and in-depth development of immune checkpoint inhibitors (ICIs) in tumor treatment, immunotherapy has emerged as a prominent approach among various anti-tumor therapies. As early as 2013, immunotherapy was recognized as the leading scientific breakthrough of the year by Science magazine \u003csup\u003e[10]\u003c/sup\u003e. In the realm of gynecological oncology, the primary immunotherapy methods currently employed include immune checkpoint inhibitors (ICIs), adoptive cellular immunotherapy (ACT), therapeutic vaccines, and cytokine therapy. Notably, immune checkpoint inhibitors (ICIs) are relatively advanced, supported by substantial clinical experience and validated through numerous clinical trials. Immune checkpoint inhibitors (ICIs) primarily restore the patient's immune system's capacity to attack cancer cells by blocking or inhibiting immune checkpoint molecules present on the surface of tumor cells. In the human body, immune checkpoint molecules function as negative regulatory entities that suppress the activity of immune cells, thereby enabling tumor cells to evade immune system detection. The role of ICIs is to obstruct these negative regulatory molecules, allowing immune cells to regain their ability to target and eliminate tumor cells. Based on their specific targets, ICIs can be categorized into three major classes of monoclonal antibodies: cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, programmed death factor 1 (PD-1) monoclonal antibodies, and programmed death factor ligand 1 (PD-L1) monoclonal antibodies. In the field of gynecological oncology, the results of the Keynote-A18 trial demonstrated that the addition of pembrolizumab increased the 2-year progression-free survival (PFS) rate of patients from 57.3\u0026ndash;67.8%, and the 3-year PFS rate improved from 56.9\u0026ndash;69.3%. An update on overall survival (OS) data indicated that the 3-year OS rate rose from 74.8\u0026ndash;82.6%\u003csup\u003e[11]\u003c/sup\u003e. The Keynote-B21 trial revealed that in high-risk postoperative patients with endometrial cancer, pembrolizumab in combination with adjuvant therapy significantly enhances disease-free survival (DFS) in the deficient mismatch repair (DMMR) population\u003csup\u003e[12]\u003c/sup\u003e. Additionally, the Atalante study illustrated that atezolizumab, when combined with platinum-based chemotherapy and bevacizumab, can elevate the 5-year survival rate of patients with platinum-sensitive recurrent epithelial ovarian cancer from 17\u0026ndash;27%\u003csup\u003e[13]\u003c/sup\u003e. As research progresses, immune checkpoint inhibitors (ICIs) are expected to play an increasingly vital role in the immunotherapy of various gynecological tumors.\u003c/p\u003e \u003cp\u003eCadonilimab is a novel PD-1/CTLA-4 bispecific antibody tumor immunotherapy drug independently developed by China Kangfang Biologics. It received marketing approval from the National Medical Products Administration of China on June 29, 2022, primarily for the treatment of patients with recurrent or metastatic cervical cancer (R/MCC) who have failed previous platinum-containing chemotherapy. Cadonilimab exhibits high affinity and operates by effectively blocking the PD-1 and CTLA-4 pathways, which in turn enhances the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ)\u003csup\u003e[14]\u003c/sup\u003e. This mechanism activates T cells to counteract immunosuppressive responses, promotes tumor-specific T cell immune activation, and ultimately inhibits tumor growth. Cadonilimab is currently being investigated not only in the field of cervical cancer but also in various studies involving other malignant tumors, including lung cancer, gastric cancer, and liver cancer. The results of the COMPASSION-03 trial indicated that during the phase 1b dose escalation phase, no dose-limiting toxicities were observed, suggesting that the overall safety profile of Cadonilimab is favorable. In the phase 2 clinical trial, Cadonilimab demonstrated significant anti-tumor activity and long-term survival benefits. Specifically, it exhibited a high overall response rate (ORR) in patients with cervical cancer. The median follow-up time for the cervical cancer cohort was 14.6 months, as assessed by the Independent Imaging Review Committee (IRRC). This committee evaluated the ORR of Cadonilimab monotherapy in patients with advanced cervical cancer who had previously failed platinum-containing chemotherapy. The ORR was found to be 32.3%, comprising a complete response (CR) of 14.1% (14 cases) and a partial response (PR) of 18.2% (18 cases)\u003csup\u003e[15]\u003c/sup\u003e. Additionally, Cadonilimab demonstrated manageable safety and robust anti-tumor activity in the treatment of advanced solid tumors. Consequently, we aim to further investigate the effectiveness and safety of Cadonilimab in treating gynecological cancer patients in real-world settings.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eIn this study, we retrospectively included patients with pathologically or cytologically confirmed diagnoses who received cadonilimab as second-line or later-line therapy from July 2022 to December 2024. The patient cohort comprised individuals with recurrent or metastatic gynecological malignancies. Inclusion criteria were as follows: pathologically or cytologically confirmed recurrent or metastatic gynecological malignancy, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0\u0026ndash;1, at least one measurable lesion, and a minimum of one cycle of cadonilimab. Exclusion criteria included: high bleeding risk, severe autoimmune disease, grade III hypertension, cardiac insufficiency, gastrointestinal dysfunction, intestinal obstruction, failure to follow up, incomplete clinical data, and the absence of measurable lesions. A total of 60 patients' clinical data were collected, summarizing demographic and clinical characteristics such as age, gender, diagnosis, stage, pathological subtype, presence of liver or brain metastasis, ECOG PS, previous treatment lines and regimens, laboratory and radiological data, as well as adverse events (AEs). The study was approved by the Ethics Committee of the Guizhou Provincial People\u0026rsquo;s Hospital. Informed consent was waived due to the retrospective nature of this study.\u003c/p\u003e \u003cp\u003eCadonilimab is administered via intravenous infusion at a recommended dose of 6 mg/kg every two weeks, continuing until either disease progression or intolerable toxicity occurs. The initial dosage is determined by the oncologist based on the patient's condition and may be adjusted in response to any intolerable side effects. The combination regimen is prescribed in accordance with the guidelines established by the National Comprehensive Cancer Network or the Chinese Society of Clinical Oncology.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssessments\u003c/h3\u003e\n\u003cp\u003eAccording to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, computerized pelvic magnetic resonance imaging was utilized to assess the patient's lesions at baseline. During the treatment period, the patient's efficacy was evaluated biweekly, with assessments conducted by the attending physician in accordance with RECIST 1.1. This version categorizes efficacy indicators into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The overall response rate (ORR) was calculated as the ratio of CR plus PR, while the disease control rate (DCR) was determined as the ratio of CR plus PR plus SD. Clinical benefit was defined as patients achieving CR, PR, or SD as their best response, whereas nonclinical benefit was characterized by patients experiencing PD as their best response. Adverse events were recorded from the first day of treatment through one month after treatment completion and were graded according to the National Cancer Institute's Adverse Event Evaluation Criteria, version 5.0.\u003c/p\u003e\n\u003ch3\u003eEnd Points\u003c/h3\u003e\n\u003cp\u003eThe primary endpoints are Objective Response Rate (ORR) and Disease Control Rate (DCR). ORR is defined as the proportion of patients whose tumor volume decreases to a predetermined value after treatment and who can maintain this minimum for the specified duration according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This includes both complete response (CR) and partial response (PR) and is expressed as the sum of these proportions. DCR, also based on RECIST 1.1, refers to the percentage of cases that achieve either a response (PR\u0026thinsp;+\u0026thinsp;CR) or stable disease (SD) after treatment, relative to the total number of evaluable cases. Secondary endpoints include progression-free survival (PFS), which is the time from the first dose to disease progression (PD) or death from any cause.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous data are presented as means with 95% confidence intervals (CIs), while categorical data are reported as frequencies or percentages (%).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 60 patients were screened between July 2022 and December 2024, including 46 patients (76.7%) with cervical cancer, 8 cases of endometrial cancer (13.3%), 1 case of endometrial adenosarcoma (1.7%), 1 case of vaginal melanoma (1.7%), 1 case of vulvar cancer (1.7%), 1 case of choriocarcinoma (1.7%)and 2 case of ovarian cancer (3.3%). 54 patients (90.0%)were in menopausal state, 32 patients(53.3%) had previous surgery, 11 patients (18.3%) had previously received chemotherapy, 23 patients(38.3%) had previously received concurrent chemoradiotherapy, 2 patient(3.3%) had previously received chemotherapy plus Targeted therapy and 3 patients (5%)had previously received radiotherapy. 15 patients (25%)had only local recurrence, and 8 patients(13.3%) had recurrence and distant metastasis. (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to the patients' use of Cadonilimab, 4 patients were excluded because they had only used Cadonilimab for one cycle and did not return to the hospital to continue treatment, making it impossible to evaluate the patient's efficacy. As of the data cutoff, 18 (32.1%) patients were still receiving treatment, and 38 (67.9%) patients had stopped treatment, of which 7 (12.5%) patients stopped due to PD and 1(2.3%) patient stopped taking medication due to hypothyroidism.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy Measures\u003c/h2\u003e \u003cp\u003eIn the Efficacy-Evaluable Population, 2 patients (3.3%) achieved a complete response (CR), 24 patients (40.0%) achieved a partial response (PR), 26 patients (43.3%) developed stable disease (SD), 4 patients (6.7%) developed progressive disease (PD) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This patient had received only one cycle of Cadonilimab treatment, and due to not returning to the hospital for further treatment and efficacy evaluation, the patient's efficacy could not be assessed.\u003c/p\u003e \u003cp\u003eAmong the responding patients, the overall response rate (ORR) was 43.3% (95% CI, 31.6 to 55.9, and the disease control rate (DCR) was 86.7% (95% CI, 75.8 to 93.1; Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the study population, there were 16 first-line patients with advanced cervical cancer, ORR was 81.3%(13/16,95% CI,57 to 93.4),DCR was 93.8%(15/16,95% CI 71.7 to 98.9); There were 30 second-line patients, ORR was 36.7%༈11/30,95% CI,21.9 to 54.5༉,DCR was 90%(27/30,95% CI 74.4 to 96.5; Table\u0026nbsp;3). Median PFS was not reached(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSafety\u003c/h3\u003e\n\u003cp\u003eIn the responder population, 41 (73.2%) patients experienced at least one treatment-related adverse event (TRAE), the most common of which were anemia (71.4%), nausea (28.6%), and myelosuppression (25%) (Table\u0026nbsp;4). 9 (16.1%) patients experienced Grade 3\u0026ndash;4 TRAEs, including 5 (8.9%) due to anemia and 4 (7.1%) due to myelosuppression. 9 (16.0%) patients experienced vomiting, 2 patients (4.7%) experienced cardiotoxic reactions. The electrocardiogram and cardiac enzyme results of these 2 patients were mildly abnormal. No treatment-related deaths occurred during treatment. Immune-related adverse reactions occurred in 11 (19.6%) patients, including 1 (1.7%) patient who developed immune osteitis and myositis, and 1 (1.7%) patient who developed immune myocarditis. 8 (14.3%) patients experienced infusion-related adverse reactions, of which 1 (1.7%) patient showed mild palpitations, chest tightness, and shortness of breath after infusion of Cadonilimab, which resolved spontaneously after rest; 3 (7.0%) patients After the infusion of Cadonilimab, not only palpitations, chest tightness, and shortness of breath occurred, but also systemic itching, rashes, etc. The patient's discomfort was relieved after anti-allergic treatment; 2 (3.6%) patients suffered from Cadonilimab infusion. After taking the monoclonal antibody, the patient developed chills and high fever, but the patient's condition improved after treatment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe GOG-240 study \u003csup\u003e[16]\u003c/sup\u003edemonstrated that patients receiving comprehensive treatment that included anti-angiogenic drugs experienced improved overall survival, with a median overall survival extension of 3.5 months, compared to those treated with chemotherapy alone. This finding establishes the basis for standard chemotherapy in combination with bevacizumab. Additionally, Lizumab is recognized as the standard first-line treatment for recurrent or metastatic cervical cancer (r/m CC). The KEYNOTE-826 study\u003csup\u003e[17]\u003c/sup\u003e investigated the efficacy of incorporating pembrolizumab, with or without bevacizumab, into chemotherapy regimens. The findings demonstrated that the addition of the PD-1 inhibitor pembrolizumab extends the first-line treatment duration for patients with cervical cancer, resulting in a median overall survival (OS) of 26.4 months. The subsequent phase III BEATcc study \u003csup\u003e[18]\u003c/sup\u003edemonstrated that, when chemotherapy and bevacizumab were combined with atezolizumab, the median progression-free survival (mPFS) for patients increased from 10.4 months to 13.7 months, while the median overall survival (mOS) improved from 22.8 months to 32.1 months. The OS of patients with advanced first-line cervical cancer is approaching 3 years. These studies are gradually improving survival times for advanced cervical cancer. The current first-line treatment options for recurrent/metastatic cervical cancer are carboplatin, paclitaxel, and bevacizumab, but the survival rate of this treatment option is still limited\u003csup\u003e[19]\u003c/sup\u003e. The recently announced COMPASSION-16 study\u003csup\u003e[20]\u003c/sup\u003e is a randomized, placebo-controlled, multi-center, double-blind phase III clinical trial. The results of the study showed that the median PFS of the Cadonilimab group and the placebo group were 13.3 months and 8.2 months, respectively. Months, the risk of disease progression or death was reduced by 38%. The current median OS has not been reached, but there is a significant benefit trend, and the study also included 28% of patients with negative PD-L1 expression (CPS\u0026thinsp;\u0026lt;\u0026thinsp;1). The KEYNOTE-826 study \u003csup\u003e[17]\u003c/sup\u003eshows that immunotherapy can significantly benefit patients with positive PD-L1 expression (CPS\u0026thinsp;\u0026ge;\u0026thinsp;1), but the benefit is not significant for patients with negative PD-L1 expression (CPS\u0026thinsp;\u0026lt;\u0026thinsp;1). Therefore, current guidelines recommend pembrolizumab. The application population of anti-PD-L1 is mainly limited to patients with positive PD-L1 expression. The COMPASSION-16 study showed that for patients with negative PD-L1 expression (CPS\u0026thinsp;\u0026lt;\u0026thinsp;1), the median progression-free survival reached 12 months (vs 8.2m), and the risk of disease progression or death was reduced by 27% (HR 0.73); For patients with positive PD-L1 expression (CPS\u0026thinsp;\u0026ge;\u0026thinsp;1), the median progression-free survival reached 13.5 months (vs 8.3m), and the risk of disease progression or death was reduced by 38% (HR 0.62). Regardless of PD-L1 expression status, all patients can benefit from Cadonilimab combination therapy. And because in clinical practice many patients have contraindications to the use of bevacizumab or are not suitable for bevacizumab, in the subgroup analysis of COMPASSION-16, for patients who are not suitable for bevacizumab, The OS of previous chemotherapy and chemotherapy\u0026thinsp;+\u0026thinsp;pembrolizumab did not reach 2 years, while the OS of chemotherapy\u0026thinsp;+\u0026thinsp;Cadonilimab was as high as 28.2 months. Cadonilimab has achieved real benefits for the entire population to a certain extent. Since 2022, Cadonilimab has shown good efficacy and safety in various malignant tumors such as liver cancer\u003csup\u003e[21]\u003c/sup\u003e, lung cancer\u003csup\u003e[22]\u003c/sup\u003e, and nasopharyngeal cancer\u003csup\u003e[23]\u003c/sup\u003e. Many dual-immunity combination studies, such as Checkmate-227 \u003csup\u003e[24, 25]\u003c/sup\u003e, have suggested that PD-1 combined with CTLA-4 can bring better survival benefits to people with negative PD-L1 expressions. In comparison to the combination therapy of anti-PD-1 monoclonal antibodies and anti-CTLA-4 monoclonal antibodies\u003csup\u003e[14]\u003c/sup\u003e, Cadonilimab exhibits significantly lower toxicity and demonstrates clear advantages in both safety and efficacy. Cadonilimab was designed with an Fc empty backbone to eliminate Fc-mediated effector functions, thereby reducing the production of pro-inflammatory cytokines such as IL-6 and IL-8. Elevated IL-6 levels in patients undergoing anti-PD-1 therapy play a critical role in immune-related adverse events (irAE), and increased IL-6 is associated with poor clinical responses to PD-1 blockade therapy. Additionally, high levels of IL-8 are linked to reduced efficacy of immune checkpoint inhibitor therapy. One study\u003csup\u003e[14]\u003c/sup\u003e found that Cadonilimab resulted in the lowest secretion of IL-6 and IL-8 compared to nivolumab and ipilimumab. This characteristic may represent a distinct mechanism of action for Cadonilimab differing from the combination of anti-PD-1 and anti-CTLA-4 antibodies, which may influence both safety and efficacy. In this study, Cadonilimab combination therapy demonstrated good therapeutic effect and controllable safety in the population with advanced gynecological malignancies. Among the population with evaluable efficacy, the ORR was 46.4% (95% CI, 34 to 59.3) and DCR 92.9% (95% CI, 83 to 97.2). In addition, there were 46 patients with advanced cervical cancer in this study, 16 of whom were treated with Cadonilimab combined with chemotherapy\u0026thinsp;\u0026plusmn;\u0026thinsp;bevacizumab as the first-line regimen, with an ORR of 81.3% (95% CI, 57 to 93.4 ), with a DCR of 93.8% (95% CI, 71.7 to 98.9). The AK104-210 trial\u003csup\u003e[15]\u003c/sup\u003e is a prospective, multi-cohort phase II clinical trial designed to evaluate the efficacy of different doses of Cadonilimab combined with platinum-based chemotherapy with or without bevacizumab in the first-line treatment of recurrent or metastatic cervical cancer. Efficacy and safety, the ORR of the three cohorts in the study were 66.7%, 68.8% and 92.3% respectively; among them, Cadonilimab (10mg Q3W)\u0026thinsp;+\u0026thinsp;chemotherapy\u0026thinsp;\u0026plusmn;\u0026thinsp;bevacizumab (A10\u0026thinsp;+\u0026thinsp;B10 cohort), the overall ORR in the entire population was 79.3%, which was higher than the entire population of pembrolizumab\u0026thinsp;+\u0026thinsp;chemotherapy\u0026thinsp;\u0026plusmn;\u0026thinsp;bevacizumab in the keynote-826 trial ORR 65.9%. The COMPASSION-16 study\u003csup\u003e[20]\u003c/sup\u003e is a randomized, double-blind, multi-center, placebo-controlled trial in patients aged 18\u0026ndash;75 years with untreated refractory, recurrent or metastatic cervical cancer, according to 1: 1 ratio random distribution The patients were enrolled in the Cadonilimab group (10 mg/kg once) or the placebo group. Both groups received platinum-containing chemotherapy, with or without bevacizumab, once every 3 weeks for a total of 6 cycles; then Maintenance treatment is given every 3 weeks for up to 2 years. In this study, the Cadonilimab group had a high tumor response rate, with an ORR of 82.9% and a DCR of 94% in the ITT population. In this study, the Cadonilimab combination treatment regimen was effective in patients with advanced first-line cervical cancer. The ORR and DCR are similar to the data of the first two studies, proving the high efficiency and high tumor response rate of Cadonilimab combined with chemotherapy\u0026thinsp;\u0026plusmn;\u0026thinsp;bevacizumab in the first-line treatment of advanced cervical cancer. In this study, 30 people used Cadonilimab combined with chemotherapy\u0026thinsp;\u0026plusmn;\u0026thinsp;bevacizumab as the second-line regimen. The ORR was 36.7% (95% CI, 21.9 to 54.5), and the DCR was 90% (87%). CI,74.4 to 96.5). AK104-201\u003csup\u003e[15]\u003c/sup\u003e is a single-arm, phase II clinical trial designed to evaluate the efficacy and safety of Cadonilimab monotherapy in the second-line treatment of recurrent or metastatic cervical cancer. The results of this study showed that in 100 patients with evaluable efficacy Among patients, the objective response rate (ORR) of Cadonilimab in the entire population was 33%. The ORR of Cadonilimab combination therapy in the second-line treatment of neck cancer is 36.7%, slightly higher than the AK104-201 study, and much higher than Keynote-158\u003csup\u003e[26]\u003c/sup\u003e, which has a similar sample size, the same number of lines of population, and a similar treatment plan as AK104-201. In the trial, the ORR of pembrolizumab in the entire population was 14.3%.\u003c/p\u003e \u003cp\u003eIn terms of safety, the treatment-related adverse events of Cadonilimab were grade 2 and below. 41 patients (73.2%) experienced at least one treatment-related adverse event (TRAE), and the incidence of greater than grade 3 was only 16.1%, which is slightly lower than the incidence of treatment-related adverse reactions used in studies of patients with advanced cervical cancer \u003csup\u003e[27]\u003c/sup\u003e. The most reported adverse events were anemia (71.4%), nausea (28.6%), and bone marrow suppression (25%). Nine patients (16.1%) experienced treatment-related adverse events (TRAEs) of grade G3-4 or higher. Following symptomatic and supportive treatment, such as blood transfusions and leukocyte elevation, the adverse reactions were significantly alleviated. Additionally, 11 patients (19.6%) developed immune-related adverse reactions of grade G1-2.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, within the collected population of gynecological malignant tumor patients, cervical cancer patients constitute the largest group, followed by those with endometrial cancer. In contrast, other cancer types, such as ovarian cancer and vaginal melanoma, each had only one case represented. This disparity limits our ability to fully assess the effectiveness and safety of Cadonilimab in treating a diverse range of gynecological tumors. Secondly, because this study is a retrospective study, the patients' genetic information and biomarkers such as PD-L1 were not collected for in-depth exploration. We will further improve this aspect in the future. Although this study has a small number of cases, a short follow-up period, and is a retrospective case analysis, it lacks prospective clinical randomized study data, and there are certain limitations in the study conclusions., but the results of this study preliminarily show that for patients with recurrent or metastatic cervical cancer, combination therapy containing Cadonilimab can achieve better clinical efficacy, and treatment-related adverse events can be controlled.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eCadonilimab with or without chemotherapy/bevacizumab had a promising antitumor activity and manageable safety profile in the treatment of recurrent/metastatic gynecological malignancies.\u003c/p\u003e \u003cp\u003e[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2024, 74(3): 229\u0026thinsp;\u0026minus;\u0026thinsp;63.\u003c/p\u003e \u003cp\u003e[2] HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022 [J]. J Natl Cancer Cent, 2024, 4(1): 47\u0026ndash;53.\u003c/p\u003e \u003cp\u003e[3] YETKIN-ARIK B, KASTELEIN A W, KLAASSEN I, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy [J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188446.\u003c/p\u003e \u003cp\u003e[4] ZHENG R S, CHEN R, HAN B F, et al. [Cancer incidence and mortality in China, 2022] [J]. Zhonghua Zhong Liu Za Zhi, 2024, 46(3): 221\u0026thinsp;\u0026minus;\u0026thinsp;31.\u003c/p\u003e \u003cp\u003e[5] CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115\u0026thinsp;\u0026minus;\u0026thinsp;32.\u003c/p\u003e \u003cp\u003e[6] MARRET G, BORCOMAN E, LE TOURNEAU C. Pembrolizumab for the treatment of cervical cancer [J]. Expert Opin Biol Ther, 2019, 19(9): 871-7.\u003c/p\u003e \u003cp\u003e[7] BESTVINA C M, FLEMING G F. Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings [J]. Oncologist, 2016, 21(10): 1250-9.\u003c/p\u003e \u003cp\u003e[8] JIANG X, TANG H, CHEN T. Epidemiology of gynecologic cancers in China [J]. J Gynecol Oncol, 2018, 29(1): e7.\u003c/p\u003e \u003cp\u003e[9] JAYSON G C, KOHN E C, KITCHENER H C, et al. Ovarian cancer [J]. The Lancet, 2014, 384(9951): 1376-88.\u003c/p\u003e \u003cp\u003e[10] MCNUTT M. Cancer Immunotherapy [J]. Science, 2013, 342(6165): 1417-.\u003c/p\u003e \u003cp\u003e[11] LORUSSO D, XIANG Y, HASEGAWA K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial [J]. Lancet, 2024, 403(10434): 1341-50.\u003c/p\u003e \u003cp\u003e[12] VAN GORP T, CIBULA D, LV W, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer [J]. Ann Oncol, 2024.\u003c/p\u003e \u003cp\u003e[13] KURTZ J E, PUJADE-LAURAINE E, OAKNIN A, et al. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial [J]. J Clin Oncol, 2023, 41(30): 4768-78.\u003c/p\u003e \u003cp\u003e[14] PANG X, HUANG Z, ZHONG T, et al. Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity [J]. MAbs, 2023, 15(1): 2180794.\u003c/p\u003e \u003cp\u003e[15] GAO X, XU N, LI Z, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial [J]. Lancet Oncol, 2023, 24(10): 1134-46.\u003c/p\u003e \u003cp\u003e[16] TEWARI K S, SILL M W, PENSON R T, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240) [J]. Lancet, 2017, 390(10103): 1654-63.\u003c/p\u003e \u003cp\u003e[17] COLOMBO N, DUBOT C, LORUSSO D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer [J]. N Engl J Med, 2021, 385(20): 1856-67.\u003c/p\u003e \u003cp\u003e[18] OAKNIN A, GLADIEFF L, MART\u0026iacute;NEZ-GARC\u0026iacute;A J, et al. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial [J]. Lancet, 2024, 403(10421): 31\u0026ndash;43.\u003c/p\u003e \u003cp\u003e[19] COHEN P A, JHINGRAN A, OAKNIN A, et al. Cervical cancer [J]. The Lancet, 2019, 393(10167): 169\u0026thinsp;\u0026minus;\u0026thinsp;82.\u003c/p\u003e \u003cp\u003e[20] WU X, SUN Y, YANG H, et al. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China [J]. Lancet, 2024, 404(10463): 1668-76.\u003c/p\u003e \u003cp\u003e[21] YUAN G, CHEN Y, ZHU P, et al. Cadonilimab (PD-1/CTLA-4) in combination with lenvatinib in unresectable hepatocellular carcinoma (uHCC): A retrospective real-world study [J]. Heliyon, 2024, 10(19): e37616.\u003c/p\u003e \u003cp\u003e[22] ZHAO Y, MA Y, FAN Y, et al. A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study) [J]. Lung Cancer, 2023, 184: 107355.\u003c/p\u003e \u003cp\u003e[23] CHEN Q Y, GUO S S, LUO Y, et al. Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study [J]. Oral Oncol, 2024, 151: 106723.\u003c/p\u003e \u003cp\u003e[24] O'BYRNE K J, LEE K H, KIM S W, et al. First-line nivolumab\u0026thinsp;+\u0026thinsp;ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients [J]. ESMO Open, 2022, 7(1): 100394.\u003c/p\u003e \u003cp\u003e[25] PAZ-ARES L, CIULEANU T E, COBO M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [J]. Lancet Oncol, 2021, 22(2): 198\u0026ndash;211.\u003c/p\u003e \u003cp\u003e[26] MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study [J]. J Clin Oncol, 2020, 38(1): 1\u0026ndash;10.\u003c/p\u003e \u003cp\u003e[27] WU X, JI J, LOU H, et al. Efficacy and safety of cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, in previously treated recurrent or metastatic (R/M) cervical cancer: a multicenter, open-label, single-arm, phase II trial (075) [J]. Gynecologic Oncology, 2022, 166: S47-S8.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"557\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eORR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eobjective response rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003edisease control rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eprogression-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ecomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003epartial response\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003estable disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eprogressive disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003econfidence intervals\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eIARC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eInternational Agency for Research on Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eICIs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eimmune checkpoint inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eACT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eadoptive cellular immunotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eCTLA-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ecytotoxic T lymphocyte antigen 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePD-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eprogrammed death factor 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePD-L1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eprogrammed death factor ligand 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eprogression-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eoverall survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003edisease-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDMMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003edeficient mismatch repair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eR/MCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003erecurrent or metastatic cervical cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eIL-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003einterleukin-2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eIFN-\u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003einterferon-\u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eIRRC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eIndependent Imaging Review Committee\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eECOG PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eEastern Cooperative Oncology Group performance status\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eadverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eRECIST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eResponse Evaluation Criteria in Solid Tumors\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003emPFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003emedian progression-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003emOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003emedian overall survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to this study. H. conceived and designed the experiments, analyzed and interpreted the data, and contributed to writing the manuscript. Z.conducted , Z. analyzed research results, Y.Z.and assisted in manuscript preparation and editing. L.L.L.B.L. \u0026nbsp; contributed to data acquisition and analysis, reviewed literature, provided intellectual input, and approved the final version of the manuscript. L. provided logistical and administrative support, ensured compliance with ethical standards, and reviewed and approved the manuscript for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of the Guizhou Provincial People\u0026rsquo;s Hospital. Informed consent was waived due to the retrospective nature of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2024, 74(3): 229-63.\u003c/li\u003e\n\u003cli\u003eHAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022 [J]. J Natl Cancer Cent, 2024, 4(1): 47-53.\u003c/li\u003e\n\u003cli\u003eYETKIN-ARIK B, KASTELEIN A W, KLAASSEN I, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy [J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188446.\u003c/li\u003e\n\u003cli\u003eZHENG R S, CHEN R, HAN B F, et al. [Cancer incidence and mortality in China, 2022] [J]. Zhonghua Zhong Liu Za Zhi, 2024, 46(3): 221-31.\u003c/li\u003e\n\u003cli\u003eCHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115-32.\u003c/li\u003e\n\u003cli\u003eMARRET G, BORCOMAN E, LE TOURNEAU C. Pembrolizumab for the treatment of cervical cancer [J]. Expert Opin Biol Ther, 2019, 19(9): 871-7.\u003c/li\u003e\n\u003cli\u003eBESTVINA C M, FLEMING G F. Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings [J]. Oncologist, 2016, 21(10): 1250-9.\u003c/li\u003e\n\u003cli\u003eJIANG X, TANG H, CHEN T. Epidemiology of gynecologic cancers in China [J]. J Gynecol Oncol, 2018, 29(1): e7.\u003c/li\u003e\n\u003cli\u003eJAYSON G C, KOHN E C, KITCHENER H C, et al. Ovarian cancer [J]. The Lancet, 2014, 384(9951): 1376-88.\u003c/li\u003e\n\u003cli\u003eMCNUTT M. Cancer Immunotherapy [J]. Science, 2013, 342(6165): 1417-.\u003c/li\u003e\n\u003cli\u003eLORUSSO D, XIANG Y, HASEGAWA K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial [J]. Lancet, 2024, 403(10434): 1341-50.\u003c/li\u003e\n\u003cli\u003eVAN GORP T, CIBULA D, LV W, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer [J]. Ann Oncol, 2024.\u003c/li\u003e\n\u003cli\u003eKURTZ J E, PUJADE-LAURAINE E, OAKNIN A, et al. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial [J]. J Clin Oncol, 2023, 41(30): 4768-78.\u003c/li\u003e\n\u003cli\u003ePANG X, HUANG Z, ZHONG T, et al. Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity [J]. MAbs, 2023, 15(1): 2180794.\u003c/li\u003e\n\u003cli\u003eGAO X, XU N, LI Z, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial [J]. Lancet Oncol, 2023, 24(10): 1134-46.\u003c/li\u003e\n\u003cli\u003eTEWARI K S, SILL M W, PENSON R T, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240) [J]. Lancet, 2017, 390(10103): 1654-63.\u003c/li\u003e\n\u003cli\u003eCOLOMBO N, DUBOT C, LORUSSO D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer [J]. N Engl J Med, 2021, 385(20): 1856-67.\u003c/li\u003e\n\u003cli\u003eOAKNIN A, GLADIEFF L, MART\u0026iacute;NEZ-GARC\u0026iacute;A J, et al. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial [J]. Lancet, 2024, 403(10421): 31-43.\u003c/li\u003e\n\u003cli\u003eCOHEN P A, JHINGRAN A, OAKNIN A, et al. Cervical cancer [J]. The Lancet, 2019, 393(10167): 169-82.\u003c/li\u003e\n\u003cli\u003eWU X, SUN Y, YANG H, et al. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China [J]. Lancet, 2024, 404(10463): 1668-76.\u003c/li\u003e\n\u003cli\u003eYUAN G, CHEN Y, ZHU P, et al. Cadonilimab (PD-1/CTLA-4) in combination with lenvatinib in unresectable hepatocellular carcinoma (uHCC): A retrospective real-world study [J]. Heliyon, 2024, 10(19): e37616.\u003c/li\u003e\n\u003cli\u003eZHAO Y, MA Y, FAN Y, et al. A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study) [J]. Lung Cancer, 2023, 184: 107355.\u003c/li\u003e\n\u003cli\u003eCHEN Q Y, GUO S S, LUO Y, et al. Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study [J]. Oral Oncol, 2024, 151: 106723.\u003c/li\u003e\n\u003cli\u003eO'BYRNE K J, LEE K H, KIM S W, et al. First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients [J]. ESMO Open, 2022, 7(1): 100394.\u003c/li\u003e\n\u003cli\u003ePAZ-ARES L, CIULEANU T E, COBO M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [J]. Lancet Oncol, 2021, 22(2): 198-211.\u003c/li\u003e\n\u003cli\u003eMARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study [J]. J Clin Oncol, 2020, 38(1): 1-10.\u003c/li\u003e\n\u003cli\u003eWU X, JI J, LOU H, et al. Efficacy and safety of cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, in previously treated recurrent or metastatic (R/M) cervical cancer: a multicenter, open-label, single-arm, phase II trial (075) [J]. Gynecologic Oncology, 2022, 166: S47-S8.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cadonilimab, Gynecological malignancies, Immunotherapy, Safety","lastPublishedDoi":"10.21203/rs.3.rs-6233481/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6233481/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e Cadonilimab, recognized as the most rapidly developed Chinese drug in the field of cervical cancer, received marketing approval in China in 2022. We conducted a study to investigate the safety and efficacy of Cadonilimab, combined with and without chemotherapy or bevacizumab treatment, in patients with recurrent / metastatic gynecological malignancies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively enrolled 60 patients with recurrent / metastatic gynecological malignant tumors, confirmed by pathology or cytology from July 2022 to December 2024. All patients received at least two cycles of Cadonilimab. The primary endpoints were the investigator-confirmed objective response rate and disease control rate according to RECIST v1.1. Secondary endpoints included progression-free survival and safety.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e56 patients were included in the efficacy analysis. In the study population, there were 16 first-line patients with advanced cervical cancer, ORR was 81.3%(13/16,95% CI,57 to 93.4),DCR was 93.8%(15/16,95% CI 71.7 to 98.9); There were 30 second-line patients, ORR was 36.7%༈11/30,95% CI,21.9 to 54.5༉,DCR was 90%(27/30,95% CI 74.4 to 96.5)。A total of 41 patients (73.2%) reported at least one treatment-related adverse event, with the most common being anemia (71.4%), nausea (28.6%), and myelosuppression (25%). 9 patients (16.1%) experienced G3-4 TRAEs. Additionally, 11 patients (19.6%) developed immune-related adverse events of G1-2. Importantly, no treatment-related deaths occurred during the study.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCadonilimab with or without chemotherapy/bevacizumab had a promising antitumor activity and manageable safety profile in the treatment of recurrent/metastatic gynecological malignancies.\u003c/p\u003e","manuscriptTitle":"Clinical efficacy and safety of Cadonilimab in the treatment of advanced gynecological malignancies: a retrospective, real-world study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-07 10:23:29","doi":"10.21203/rs.3.rs-6233481/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-14T14:00:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-12T03:25:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232445722927078874622487328889268212308","date":"2025-04-09T08:20:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T01:02:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316544075063352733486701966794953563626","date":"2025-04-07T02:13:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5294891575562214935381490363510385460","date":"2025-04-05T00:39:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-04T08:00:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-03T23:09:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-03T15:36:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-03T10:08:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-04-03T10:07:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"49baff40-1b8b-40d4-b725-d560cd143268","owner":[],"postedDate":"April 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:33:31+00:00","versionOfRecord":{"articleIdentity":"rs-6233481","link":"https://doi.org/10.1186/s12885-025-14603-0","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2025-08-19 16:29:13","publishedOnDateReadable":"August 19th, 2025"},"versionCreatedAt":"2025-04-07 10:23:29","video":"","vorDoi":"10.1186/s12885-025-14603-0","vorDoiUrl":"https://doi.org/10.1186/s12885-025-14603-0","workflowStages":[]},"version":"v1","identity":"rs-6233481","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6233481","identity":"rs-6233481","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}