Sunitinib in patients with favorable and intermediate risk metastatic renal cell carcinoma – Lithuanian National Cancer Institute experience

Sunitinib in patients with favorable and intermediate risk metastatic renal cell carcinoma – Lithuanian National Cancer Institute experience | 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 Sunitinib in patients with favorable and intermediate risk metastatic renal cell carcinoma – Lithuanian National Cancer Institute experience Algirdas Zalimas, Vincas Urbonas, Daiva Dabkeviciene, Jonas Purvaneckas, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2032562/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction and Objectives Sunitinib, according to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommendations, is one of the recommended regimens for favorable and intermediate risk metastatic renal cell carcinoma (mRCC) patients. Our objective was to evaluate sunitinib efficacy as a first-line treatment for mRCC patients with favorable / intermediate prognostic risk in a real-world setting. Materials and Methods Patients with diagnosed mRCC and confirmed as appropriate candidates for the first-line systemic treatment were included in the retrospective study. The prognostic risk was evaluated according to the model of International Metastatic RCC Database Consortium (IMDC). Patients received sunitinib as a first-line treatment. Results A total of 94 patients were enrolled from 2019 to the 2020 year. 67 patients were included for the detailed analysis. The median age at diagnosis was 62 years. Majority of patients had clear cell renal carcinoma with prior nephrectomy. Half of patients had more than 3 metastatic sites. Metastasectomy was performed for one third of the patients. Median progression-free survival (PFS) was 23.4 (95% CI: 17.3-29.5), and median overall survival (OS) was 66 months (95% CI: 44.9-87.1). The age over 60 years was significant negative predictor for PFS and OS. Regarding IMDC model for disease risk prediction, the number of two risk factors in the intermediate risk group was a significant predictor for a shorter response to the first-line therapy. Conclusion In everyday clinical practice, sunitinib is an effective systemic therapy for favorable/intermediate risk groups mRCC patients. This tyrosine kinase inhibitor (TKI) can be used as a first-line treatment in this group of patients, especially in countries where novel systemic treatment modalities are not available yet. Renal cell carcinoma metastasis sunitinib risk groups Figures Figure 1 Figure 2 Introduction Kidney cancer is one of the most aggressive tumors of the urogenital system. Clinically most of the renal cell carcinoma (RCC) cases are asymptomatic and discovered incidentally, especially in the early stages [1]. Unfortunately, up to 30% of patients still present with metastatic RCC (mRCC) disease [2]. The prognosis for mRCC patients has been historically poor, 5 years survival rate is less than 10 % [3]. Systemic therapy is the primary treatment strategy for mRCC. Previously, before the introduction of targeted therapies, cytokine-based therapy with interferon-alfa (IFN -α) and/or interleukin-2 (IL-2) was considered as a standard first-line treatment for patients with mRCC. However, the response rates were low (approximately 15%), OS was limited to a median of 13 months, and treatment-related toxicities restricted their wider usage [4]. In addition, previous studies of other therapies for cytokine-refractory patients with RCC were unable to show benefits [5]. Nowadays, for the mRCC treatment, first-line agents are multitargeted tyrosine kinase inhibitors (TKIs) such as sunitinib [6] and pazopanib [7], [8]. They can be used alone or in combination with immunotherapy. Recently, in the past 4 years six new immunotherapy (IO) drug combinations, such as IO-TKI and IO-IO regimens, have demonstrated significant clinical efficacy compared to the standard of care of vascular endothelial growth factor (VEGF) -TKI sunitinib monotherapy [9]. Sunitinib is TKI of platelet-derived growth factor (PDGF) receptors alfa and beta, VEGF receptors 1-3 and other tyrosine kinases that stimulate angiogenesis. This orally available, small molecule has been successfully used globally for the management of mRCC for over 14 years [6]. It is presently considered as a recommended first-line treatment modality for mRCC patients of favorable and intermediate risk groups according to the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) guidelines [4, 5]. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model for survival prediction in mRCC patients uses six variables - Karnofsky performance status, time of diagnosis to systemic treatment, platelet and neutrophil counts, hemoglobin count, calcium concentration in serum - for patients’ stratification into favorable (no risk factors), intermediate (1 or 2 risk factors) and poor risk (3 and more risk factors) prognostic groups [10]. This model is widely used in clinical practice and was used in our study for sunitinib efficacy assessment. Based on the fact that Lithuania has one of the highest morbidity and mortality rates of kidney cancer in Europe [11] the main objective was to evaluate sunitinib as a first-line treatment for mRCC patients corresponding to favorable or intermediate prognostic groups. Methods Study design and patients Between January 1, 2019 and December 31, 2020, 94 mRCC patients were treated at the National Cancer Institute (NCI), Vilnius, Lithuania. A retrospective study was performed on 67 patients treated with the first line sunitinib in the metastatic disease setting. 27 patients were excluded from the study due to other treatment modalities mainly pazopanib, lack of data related to IMDC, missing blood tests or lost patient monitoring (Consort diagram, Fig. 1). The study population comprised of patients aged 18 and over years with morphologically confirmed diagnosis of mRCC (mainly clear cell carcinoma) having at least one measurable target according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. According to IMDC, the patients were divided into favorable and intermediate risk groups. The intermediate risk group was formed according to the number of risk factors (1 or 2), while favorable risk group had no IMDC risk factors. According to metastasis number the patients were divided into two groups: higher disease burden (≥ metastases) and lower disease burden (< 3 metastases). Sunitinib was as a first-line treatment with dose of 50 mg daily in cycles of 14 days on and 7 days off or 28 days on and 14 days off every 6 weeks. Second-line treatment with axitinib, cabozantinib or nivolumab was administered in case of progression of the first-line treatment. OS was defined as the time from treatment with sunitinib initiation until death or lost on follow-up. Progression free survival (PFS) was defined as the time from treatment with sunitinib beginning until disease progression or the start date of a second line treatment. First patient included in prospective evaluation started treatment with sunitinib on 14, December, 2012. The data cut-off for final evaluation was May 1, 2022. Statistical analysis The treatment efficacy measures, including PFS and OS, were determined. Survival outcomes were described using median time for PFS and OS with 95% CI. The statistical difference between the survival outcomes was determined using Cox regression analysis and 95% CI was applied for hazard ratio (HR) calculations. Also, Kaplan-Meier curves were used for the visualization of data, and trends or statistically significant changes in outcomes were represented as graphs. Differences were considered statistically significant when P-value was < 0.05. The data were analyzed using software: IBM SPSS Statistics 21, R version 4.0.3 and RStudio 2022.07.1. Results Patients In this retrospective single-center study 67 patients with mRCC on first-line sunitinib therapy were analyzed. Median age of mRCC patients was 62 years (interquartile range, 56-67 years). The majority of patients were males (52 out of 67; 78%). At the beginning of treatment all patients had Eastern Cooperative Oncology Group (ECOG) score ≤ 2. The most mRCC patients included into analysis started treatment with sunitinib 50 mg/d PO on schedule 2/1 or 4/2. In terms of clinical characteristics, the cohort consisted of patients diagnosed as follows: 60% with stage T3 / T4, 33% with advanced metastases (M1), 71% with high cell differentiation score (G2-G4). Majority of patients had clear cell renal carcinoma (94%) with prior nephrectomy (94%). Regarding disease volume, 48% of patients had more than 3 metastatic sites (Table 1). The main metastatic localizations were lungs (70 %) or/and lymph nodes (27 %) or/and bones (31 %). Metastasectomy was performed for one third of the patients. Treatment efficacy Overall, median response time to sunitinib therapy was 23.4 months (95% CI, 17.3-29.5 months) and a median OS was 66.0 months (95% CI, 44.9-87.1 months). PFS and OS according to clinic-pathological and demographic characteristics are presented in Table 2 and the Kaplan-Meier curves are presented in Fig. 2A, 2C and 2D. Regarding IMDC risk prognostic groups and related risk factors, PFS and OS are presented in Table 2 and the Kaplan-Meier curves are presented in Fig. 2B. The age over 60 years and the number of IMDC risk factors in a prognostic risk group were the main predictors for significantly shorter response to therapy with sunitinib. In line, patients classified to IMDC intermediate risk group had shorter PFS and HR=1.6 in comparison with patient group lacking IMDC risk factors. The age over 60 years was significant predictor not only for the shorter response to therapy but also for the worse OS. As was expected, patients with the higher disease burden had a trend for the shorter OS relatively to patients with the lower disease burden. It should be noted that the patients with two IMDC risk factors in the intermediate risk prognostic group had 1.7 times higher HR for OS in comparison with the patients lacking these negative ones in favorable risk prognostic group. However, the length of OS in the intermediate risk prognostic group with one IMDC risk factor was comparable to the favorable risk prognostic group. Table 1. Clinico-pathological and demographical characteristics of study cohort Cohort size 67 Age at enrollment, years: up to 60 60 and over 27 40 Gender: man woman 52 15 Tumor stage: T1 T2 T3 T4 19 8 37 3 Node stage: N0 N1 N2 Nx 56 9 0 2 Metastases stage: M0 M1 Mx 44 22 1 Tumor grade: G1 G2 G3 G4 unknown 4 18 30 1 14 Histology: ccRCC Papillary Chromophobe 63 3 1 Metastasis: <3 ≥3 35 32 Nephrectomy Biopsy 63 4 First-line treatment Sunitinib 67 Second-line treatment Axitinib Cabozantinib Nivolumab Denosumab 32 6 7 1 Table 2. Survival time and Cox regression analysis to assess significant factors associated with survival outcomes. NA-not applicable; N/N-number/number; HR - hazard ratio; CI - Confidence Interval; PFS, months OS, months Subgroup Cases: Total N/N of events Time, median (95% CI) HR (95% CI), P Cases: Total N/N of events Time, median (95% CI) HR (95% CI), P Overall 67/53 23.4 (17.3-29.5) 67/32 66.0 (44.9-87.1) Age at enrollment, years: up to 60 60 and over 27/18 40/35 27.4 (7.0 – 47.8) 21.2 (16.4-25.9) Ref. 2.04 (1.1-3.7), 0.02 27/8 40/24 79.0 (58.8-99.2) 44.0 (29.6-58.4) Ref. 2.6 (1.1-5.8), 0.02 Sex: male female 52/41 15/12 22.0 (17.8 – 26.3) 32.1 (3.6 – 60.7) Ref. 0.8 (0.39-1.5), 0.42 52/26 15/6 58.0 (38.2 - 77.8) NA (NA) Ref. 0.53 (0.20-1.4), 0.19 Metastasis: <3 ≥3 35/27 32/26 24.5 (17.5 – 31.5) 20.5 (14.5 – 26.6) Ref. 1.4 (0.8-2.4), 0.24 35/14 32/18 70.0 (52.8 – 87.2) 44.0 (17.3 – 70.7) Ref. 1.8 (0.91-3.7), 0.09 IMDC risk group: favorable intermediate 28/20 39/33 26.0 (16.6 – 35.4) 20.5 (11.8 – 29.2) Ref. 1.6 (0.9-2.8), 0.13 28/13 39/19 68.0 (29.7 – 106.3) 66.0 (31.8 – 100.15) Ref. 1.16 (0.57-2.3), 0.69 Number of IMDS risk factors: 0 1 2 28/20 25/21 14/12 26.0 (16.6 – 35.4) 27.4 (13.6 – 41.2) 16.2 (14.3 – 18.1) Ref. 1.4 (0.7-2.6), 0.32 2.1 (1.0-4.5), 0.048 28/13 25/12 14/7 68.0 (29.7 – 106.3) 66.0 (49.8 – 82.2) 36.0 (12.9 – 59.1) Ref. 1 0.97 (0.44-2.1), 0.94 1.74 (0.68-4.4), 0.24 Prior nephrectomy: Yes No 63/50 4/3 22.9 (17.7 - 28.0) 37.6 (0.8 – 74.4) Ref. 0.67 (0.21– 2.2) 0.51 63/30 4/2 66.0 (45.8-86.2) 30.0 (NA) Ref. 1.1 (0.25– 4.4), 0.93 Discussion Despite new treatment possibilities included in the latest ESMO and NCCN guidelines, sunitinib along with other TKI pazopanib are presented as a recommended first-line treatment modality for mRCC patients with favorable or intermediate risk prognostic factors [4,5]. Sunitinib demonstrated sufficient efficacy and safety in mRCC patients and even if it is not the newest treatment modality for mRCC patients, it still can be considered for mRCC patients if newer treatment combinations are not accessible, or patients are not good candidates for immuno-oncology treatment due to their comorbidities. Our retrospective data proved the efficacy and safety of sunitinib in patients with mRCC favorable and intermediate risk groups according to IMDC classification. The median PFS in our patient’s population with IMDC favorable and intermediate risk were 26.0 months (95% CI, 16.6-35.4 months) and 20.5 months (95% CI, 11.8-29.2 months), respectively. Similar results were shown in ADONIS observational trial [12]. In this trial mRCC patients were treated with first line sunitinib and efficacy were evaluated according to IMDC and MSKCC criteria. The median PFS in ADONIS trial for patients with favorable and intermediate risk were 23.8 months (95% CI, 13.5-28.5 months) and 12.2 months (95% CI, 8.7-19.8 months), respectively. Higher efficacy results in our retrospective analysis for patients with intermediate risk could be explained by differences in study design and patient population. In our real-world mRCC patient’s population, the median OS for patients with favorable risk was 68.0 months (95% CI, 29.7-106.3 months). OS results for the same patient’s population in ADONIS trial [12] was similar (67.4 months (95% CI, 46.3-102 months) and comparable to OS data presented by Schwab et al. (72.0 months), however in retrospective analysis done by Schwab et al. mRCC patients were treated not only with sunitinib but also with other TKIs, mTOR inhibitors [13]. Majority of patients (94%) in our study had prior cytoreductive nephrectomy (CN) and it is well known that CN may provide an OS benefit in selected mRCC patient’s population [14,15]. Metastasis volume, count and site are important assessing response to the treatment [16]. Our data shows that patients diagnosed with more than 3 metastases had lower OS compared to patients with 3 and less metastases (44.0 months versus 70.0 months). It should be mentioned that metastasectomy is associated with improved oncologic outcomes and plays an important role in patient survival. Six studies reported a significantly longer median OS or cancer-specific survival (CSS) following complete metastasectomy (the median value for OS or CSS was 40.75 months, range 23–122 months) compared with incomplete and/or no metastasectomy (the median value for OS or CSS was 14.8 months, range 8.4–55.5 months) [17-22]. Three studies reported the complex treatment of RCC metastases in the lung [23], liver [24] and pancreas [25], respectively. The lung metastases study reported a significantly higher median OS for metastasectomy vs. medical therapy (for both targeted therapy and immunotherapy) [23-25]. Similarly, the liver and pancreas metastases study reported a significantly higher median OS and five-year OS for metastasectomy vs. no metastasectomy [23,25]. In our cohort, 30% of patients underwent metastasectomy and this factor possibly had a positive impact on OS. Undoubtedly, an appropriate systemic treatment choice strategy results in prolonged patient survival [26, 27]. According to our retrospective data, second-line therapy after sunitinib was mainly axitinib (48 %) and other treatment modalities (cabozantinib, nivolumab). One of explanations for the prolonged OS in our patient’s population within each risk group in comparison with pivotal phase III sunitinib trial [28], might be the benefit obtained from the second-line treatment with the newer systemic therapies such as axitinib, cabozantinib, nivolumab. Nowadays, immunotherapy-based drug combinations, such as IO-TKI and IO-IO regimens, are widely used and proved their benefit and significant clinical efficacy [29]. The phase III trials as CheckMate 214 (nivolumab plus ipilimumab), CheckMate 9ER (Nivolumab plus cabozantinib), KEYNOTE-426 (Pembrolizumab plus axitinib), IMmotion151 (Atezolizumab plus bevacizumab) showed a superiority of over sunitinib with OS up to 47 months, focused on the IMDC intermediate- and poor-risk population [30]. The median OS with nivolumab plus ipilimumab was 74 months for favorable- risk patients [31]. Combinations of immunotherapies and antiangiogenetic agents have improved patient outcomes, but sunitinib still shows sufficient efficacy and can be used especially in countries where novel combinations not reimbursed yet. Limitations of our study include the retrospective data analysis, relatively small patient’s cohort, not presented treatment related adverse events. However, such everyday clinical practice-based data provide further rationale on the use of sunitinib for mRCC with low to intermediate risk criteria. Conclusion Everyday clinical practice-based data shows sufficient efficacy of sunitinib in mRCC patients with favorable and intermediate risk according to IMDC. Favorable clinical responses can be achieved using sunitinib as a first-line treatment, especially in countries where novel combinations such as nivolumab/cabozantinib, pembrolizumab/axitinib, nivolumab/ipilimumab are not reimbursed yet. Declarations Ethics approval The retrospective analysis of available patient data was performed in accordance with the declaration of Helsinki and approved by the institutional ethics committee (Vilnius University Faculty of Medicine, ethics protocol number 2019/2˗1074˗586). Consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to privacy legislation but are available from the corresponding author on reasonable request. Funding Not applicable. Authors ’ contribution AZ: data collection, literature review and manuscript preparation; Others: statistical analysis, revising manuscript critically for important intellectual content, have made substantial contributions to conception and design. All authors are supported by the Vilnius University. All authors read and approved the final manuscript. 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Ljungberg B, Albiges L, Bedke J, Bex A, Capitanio U, Giles RH, Hora M, Klatte T, Lam T, Marconi L, et al. Renal Cell Carcinoma. EAU 2022 guidelines. Motzer RJ, Tannir NM, McDermott DF, Burotto M, Choueiri TK, Hammers HJ, Plimack ER, Porta CG, George S, Powles TB, et al. Conditional survival and 5-year follow-up in CheckMate 214: First-line nivolumab + ipilimumab (N + I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC). Ann Oncol. 2021;32:68. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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-2032562","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":137779904,"identity":"15a47553-3d6c-4b9e-9804-b5d64baaf4ec","order_by":0,"name":"Algirdas Zalimas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYDACdgaGAyCajxlEVgAxM3MDfi3MUC1sYC1nQCKMhLWAARuIYGwDk/i18DezXzz4g6FOno2dO/Hjz3m10fztQC0/Krbh1CJxmKfgMA8Dm2EbM+9mad5tx3NnHGZsYOw5cxu3NYd5Eg4zMPAwArVskGbcdiy3AaiFmbENtxZ5oBagwyTsQbb8/DnnWO58QloMDrMfOMDDYJAI1LJNgrehJncDIS2GQI8c5jFISAZpseY5diB3I1DLQXx+kTve/vjjj4o6237+s5tv/qipy513/vDBBz8q8HifgccA6DxEaIDJA3jUAwH7A2ReHX7Fo2AUjIJRMCIBAJqfVnFHUS6vAAAAAElFTkSuQmCC","orcid":"","institution":"Institute of Biosciences, Life Sciences Center, Vilnius University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Algirdas","middleName":"","lastName":"Zalimas","suffix":""},{"id":137779905,"identity":"975b2372-d532-4c3a-b471-3d97db2a3705","order_by":1,"name":"Vincas Urbonas","email":"","orcid":"","institution":"National cancer institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Vincas","middleName":"","lastName":"Urbonas","suffix":""},{"id":137779906,"identity":"2b06c4bb-7387-4d72-b5f9-e80d02ad103f","order_by":2,"name":"Daiva Dabkeviciene","email":"","orcid":"","institution":"National cancer institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daiva","middleName":"","lastName":"Dabkeviciene","suffix":""},{"id":137779907,"identity":"d2c7008e-3c2a-46f0-ba67-4acc23ec3b73","order_by":3,"name":"Jonas Purvaneckas","email":"","orcid":"","institution":"Vilnius University, Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jonas","middleName":"","lastName":"Purvaneckas","suffix":""},{"id":137779908,"identity":"60c6165b-9b19-477d-b003-0054ed2e0a95","order_by":4,"name":"Albertas Ulys","email":"","orcid":"","institution":"National cancer institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Albertas","middleName":"","lastName":"Ulys","suffix":""},{"id":137779909,"identity":"ba776b2a-1d75-4681-b00a-1903dfd3ff08","order_by":5,"name":"Sonata Jarmalaite","email":"","orcid":"","institution":"Institute of Biosciences, Life Sciences Center, Vilnius University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sonata","middleName":"","lastName":"Jarmalaite","suffix":""}],"badges":[],"createdAt":"2022-09-05 07:14:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2032562/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2032562/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":26883665,"identity":"d6c8b125-f026-4420-9aef-619d1d28a143","added_by":"auto","created_at":"2022-09-23 14:48:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73095,"visible":true,"origin":"","legend":"\u003cp\u003eSelection, Treatment, and Follow-up of the Patients. A retrospective descriptive study was performed with patients treated due to metastatic kidney cancer at the National Cancer Institute, Dept. of Urology in the period from 2019 to 2020. Prognostic risk was evaluated according to International Metastatic RCC Database Consortium (IMDC). Overall survival and progression-free survival were analyzed.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2032562/v1/c6426263ecffe227159ebfc7.png"},{"id":26883664,"identity":"1b09c249-c71d-404e-bca9-2baa441086ca","added_by":"auto","created_at":"2022-09-23 14:48:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":83422,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival and overall survival for sunitinib therapy in patients with mRCC. Graphs are supplied to disclose significant changes in PFS and OS by age (A, C) and by IMDC risk factors (B, D).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2032562/v1/808f588476460e761f7d2ad9.png"},{"id":29128733,"identity":"627e88cf-a828-4241-97db-6c6f0e3ed935","added_by":"auto","created_at":"2022-11-16 10:29:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":417136,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2032562/v1/0a0ed6a9-3c41-4468-ab5a-087e6aa047a6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sunitinib in patients with favorable and intermediate risk metastatic renal cell carcinoma – Lithuanian National Cancer Institute experience","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKidney cancer is one of the most aggressive tumors of the urogenital system. Clinically most of the renal cell carcinoma (RCC) cases are asymptomatic and discovered incidentally, especially in the early stages [1]. Unfortunately, up to 30% of patients still present with metastatic RCC (mRCC) disease [2]. The prognosis for mRCC patients has been historically poor, 5 years survival rate is less than 10 % [3]. Systemic therapy is the primary treatment strategy for mRCC. Previously, before the introduction of targeted therapies, cytokine-based therapy with interferon-alfa (IFN -\u0026alpha;) and/or interleukin-2 (IL-2) was considered as a standard first-line treatment for patients with mRCC. However, the response rates were low (approximately 15%), OS was limited to a median of 13 months, and treatment-related toxicities restricted their wider usage [4]. In addition, previous studies of other therapies for cytokine-refractory patients with RCC were unable to show benefits [5]. Nowadays, for the mRCC treatment, first-line agents are multitargeted tyrosine kinase inhibitors (TKIs) such as sunitinib [6] and pazopanib [7], [8]. They can be used alone or in combination with immunotherapy. Recently, in the past 4 years six new immunotherapy (IO) drug combinations, such as IO-TKI and IO-IO regimens, have demonstrated significant clinical efficacy compared to the standard of care of vascular endothelial growth factor (VEGF) -TKI sunitinib monotherapy [9].\u003c/p\u003e\n\u003cp\u003eSunitinib is TKI of platelet-derived growth factor (PDGF) receptors alfa and beta, VEGF receptors 1-3 and other tyrosine kinases that stimulate angiogenesis. This orally available, small molecule has been successfully used globally for the management of mRCC for over 14 years [6]. It is presently considered as a recommended first-line treatment modality for mRCC patients of favorable and intermediate risk groups according to the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) guidelines [4, 5]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model for survival prediction in mRCC patients uses six variables - Karnofsky performance status, time of diagnosis to systemic treatment, platelet and neutrophil counts, hemoglobin count, calcium concentration in serum - for patients\u0026rsquo; stratification into favorable (no risk factors), intermediate (1 or 2 risk factors) and poor risk (3 and more risk factors) prognostic groups [10]. This model is widely used in clinical practice and was used in our study for sunitinib efficacy assessment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on the fact that Lithuania has one of the highest morbidity and mortality rates of kidney cancer in Europe [11] the main objective was to evaluate sunitinib as a first-line treatment for mRCC patients corresponding to favorable or intermediate prognostic groups.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween January 1, 2019 and December 31, 2020, 94 mRCC patients were treated at the National Cancer Institute (NCI), Vilnius, Lithuania. A retrospective study was performed on 67 patients treated with the first line sunitinib in the metastatic disease setting. 27 patients were excluded from the study due to other treatment modalities mainly pazopanib, lack of data related to IMDC, missing blood tests or lost patient monitoring (Consort diagram, Fig. 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study population comprised of patients aged 18 and over years with morphologically confirmed diagnosis of mRCC (mainly clear cell carcinoma) having at least one measurable target according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. According to IMDC, the patients were divided into favorable and intermediate risk groups. The intermediate risk group was formed according to the number of risk factors (1 or 2), while favorable risk group had no IMDC risk factors. According to metastasis number the patients were divided into two groups: higher disease burden (≥\u0026nbsp;metastases) and lower disease burden (\u0026lt; 3 metastases).\u003c/p\u003e\n\u003cp\u003eSunitinib was as a first-line treatment with dose of 50 mg daily in cycles of 14 days on and 7 days off or 28 days on and 14 days off every 6 weeks. Second-line treatment with axitinib, cabozantinib or nivolumab was administered in case of progression of the first-line treatment. \u0026nbsp;OS was defined as the time from treatment with sunitinib initiation until death or lost on follow-up. Progression free survival (PFS) was defined as the time from treatment with sunitinib beginning until disease progression or the start date of a second line treatment. First patient included in prospective evaluation started treatment with sunitinib on 14, December, 2012. The data cut-off for final evaluation was May 1, 2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe treatment efficacy measures, including PFS and OS, were determined. Survival outcomes were described using median time for PFS and OS with 95% CI. The statistical difference between the survival outcomes was determined using Cox regression analysis and 95% CI was applied for hazard ratio (HR) calculations. Also, Kaplan-Meier curves were used for the visualization of data, and trends or statistically significant changes in outcomes were represented as graphs. Differences were considered statistically significant when P-value was \u0026lt; 0.05. The data were analyzed using software: IBM SPSS Statistics 21, R version 4.0.3 and RStudio 2022.07.1.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this retrospective single-center study 67 patients with mRCC on first-line sunitinib therapy were analyzed. Median age of mRCC patients was 62 years (interquartile range, 56-67 years). The majority of patients were males (52 out of 67; 78%). At the beginning of treatment all patients had Eastern Cooperative Oncology Group (ECOG) score \u0026le; 2. The most mRCC patients included into analysis started treatment with sunitinib 50 mg/d PO on schedule 2/1 or 4/2. In terms of clinical characteristics, the cohort consisted of patients diagnosed as follows: 60% with stage T3 / T4, 33% with advanced metastases (M1), 71% with high cell differentiation score (G2-G4). Majority of patients had clear cell renal carcinoma (94%) with prior nephrectomy (94%). Regarding disease volume, 48% of patients had more than 3 metastatic sites (Table 1). The main metastatic localizations were lungs (70 %) or/and lymph nodes (27 %) or/and bones (31 %). Metastasectomy was performed for one third of the patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment efficacy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, median response time to sunitinib therapy was 23.4 months (95% CI, 17.3-29.5 months) and a median OS was 66.0 months (95% CI, 44.9-87.1 months). PFS and OS according to clinic-pathological and demographic characteristics are presented in Table 2 and the Kaplan-Meier curves are presented in Fig. 2A, 2C and 2D. Regarding IMDC risk prognostic groups and related risk factors, PFS and OS are presented in Table 2 and the Kaplan-Meier curves are presented in Fig. 2B.\u003c/p\u003e\n\u003cp\u003eThe age over 60 years and the number of IMDC risk factors in a prognostic risk group were the main predictors for significantly shorter response to therapy with sunitinib. In line, patients classified to IMDC intermediate risk group had shorter PFS and HR=1.6 in comparison with patient group lacking IMDC risk factors. The age over 60 years was significant predictor not only for the shorter response to therapy but also for the worse OS. As was expected, patients with the higher disease burden had a trend for the shorter OS relatively to patients with the lower disease burden. It should be noted that the patients with two IMDC risk factors in the intermediate risk prognostic group had 1.7 times higher HR for OS in comparison with the patients lacking these negative ones in favorable risk prognostic group. However, the length of OS in the intermediate risk prognostic group with one IMDC risk factor was comparable to the favorable risk prognostic group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Clinico-pathological and demographical characteristics of study cohort\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eCohort size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eAge at enrollment, years:\u003c/p\u003e\n \u003cp\u003eup to 60\u003c/p\u003e\n \u003cp\u003e60 and over\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eGender:\u003c/p\u003e\n \u003cp\u003eman\u003c/p\u003e\n \u003cp\u003ewoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eTumor stage:\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eNode stage:\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eNx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eMetastases stage:\u003c/p\u003e\n \u003cp\u003eM0\u003c/p\u003e\n \u003cp\u003eM1\u003c/p\u003e\n \u003cp\u003eMx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eTumor grade:\u003c/p\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003cp\u003eG4\u003c/p\u003e\n \u003cp\u003eunknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eHistology:\u003c/p\u003e\n \u003cp\u003eccRCC\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePapillary\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eChromophobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eMetastasis:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003cp\u003e\u0026ge;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eNephrectomy\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBiopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eFirst-line treatment\u003c/p\u003e\n \u003cp\u003eSunitinib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"57.556270096463024%\"\u003e\n \u003cp\u003eSecond-line treatment\u003c/p\u003e\n \u003cp\u003eAxitinib\u003c/p\u003e\n \u003cp\u003eCabozantinib\u003c/p\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.443729903536976%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Survival time and Cox regression analysis to assess significant factors associated with survival outcomes. NA-not applicable; N/N-number/number; HR - hazard ratio; CI - Confidence Interval;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePFS, months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eOS, months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSubgroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCases:\u003c/p\u003e\n \u003cp\u003eTotal N/N of events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTime, median (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI), P\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCases:\u003c/p\u003e\n \u003cp\u003eTotal N/N of events\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTime, median (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI), P\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23.4 (17.3-29.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67/32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66.0 (44.9-87.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge at enrollment, years:\u003c/p\u003e\n \u003cp\u003eup to 60\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60 and over\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27/18\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27.4\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7.0 \u0026ndash; 47.8)\u003c/p\u003e\n \u003cp\u003e21.2\u003c/p\u003e\n \u003cp\u003e(16.4-25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e2.04\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.1-3.7), 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27/8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40/24\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e79.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(58.8-99.2)\u003c/p\u003e\n \u003cp\u003e44.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(29.6-58.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e2.6\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.1-5.8), 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex:\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52/41\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(17.8 \u0026ndash; 26.3)\u003c/p\u003e\n \u003cp\u003e32.1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(3.6 \u0026ndash; 60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.8\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.39-1.5), 0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52/26\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15/6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(38.2 - 77.8)\u003c/p\u003e\n \u003cp\u003eNA (NA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003cp\u003e(0.20-1.4), 0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMetastasis:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026ge;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35/27\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24.5 (17.5 \u0026ndash; 31.5)\u003c/p\u003e\n \u003cp\u003e20.5 (14.5 \u0026ndash; 26.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.4 (0.8-2.4), 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35/14\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32/18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70.0 (52.8 \u0026ndash; 87.2)\u003c/p\u003e\n \u003cp\u003e44.0 (17.3 \u0026ndash; 70.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.8 (0.91-3.7), 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIMDC risk group:\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003efavorable\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eintermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28/20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39/33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26.0 (16.6 \u0026ndash; 35.4)\u003c/p\u003e\n \u003cp\u003e20.5 (11.8 \u0026ndash; 29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.6 (0.9-2.8), 0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28/13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39/19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68.0 (29.7 \u0026ndash; 106.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e66.0 (31.8 \u0026ndash; 100.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.16 (0.57-2.3), 0.69\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNumber of IMDS risk factors:\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28/20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25/21\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26.0\u003c/p\u003e\n \u003cp\u003e(16.6 \u0026ndash; 35.4)\u003c/p\u003e\n \u003cp\u003e27.4\u003c/p\u003e\n \u003cp\u003e(13.6 \u0026ndash; 41.2)\u003c/p\u003e\n \u003cp\u003e16.2\u003c/p\u003e\n \u003cp\u003e(14.3 \u0026ndash; 18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.4\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.7-2.6), 0.32\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.0-4.5), 0.048\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28/13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25/12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14/7\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(29.7 \u0026ndash; 106.3)\u003c/p\u003e\n \u003cp\u003e66.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(49.8 \u0026ndash; 82.2)\u003c/p\u003e\n \u003cp\u003e36.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(12.9 \u0026ndash; 59.1)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.97\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.44-2.1), 0.94\u003c/p\u003e\n \u003cp\u003e1.74\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.68-4.4), 0.24\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior nephrectomy:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63/50\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4/3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22.9\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(17.7 - 28.0)\u003c/p\u003e\n \u003cp\u003e37.6\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.8 \u0026ndash; 74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.67\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.21\u0026ndash; 2.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63/30\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e66.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(45.8-86.2)\u003c/p\u003e\n \u003cp\u003e30.0 (NA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(0.25\u0026ndash; 4.4), 0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eDespite new treatment possibilities included in the latest ESMO and NCCN guidelines, sunitinib along with other TKI pazopanib are presented as a recommended first-line treatment modality for mRCC patients with favorable or intermediate risk prognostic factors\u0026nbsp;[4,5]. \u0026nbsp;Sunitinib demonstrated sufficient efficacy and safety in mRCC patients and even if it is not the newest treatment modality for mRCC patients, it still can be considered for mRCC patients if newer treatment combinations are not accessible, or patients are not good candidates for immuno-oncology treatment due to their comorbidities.\u003c/p\u003e\n\u003cp\u003eOur retrospective data proved the efficacy and safety of sunitinib in patients with mRCC favorable and intermediate risk groups according to IMDC classification. The median PFS in our patient\u0026rsquo;s population with IMDC favorable and intermediate risk were 26.0 months (95% CI, 16.6-35.4 months) and 20.5 months (95% CI, 11.8-29.2 months), respectively. Similar results were shown in ADONIS observational trial [12]. In this trial mRCC patients were treated with first line sunitinib and efficacy were evaluated according to IMDC and MSKCC criteria. The median PFS in ADONIS trial for patients with favorable and intermediate risk were 23.8 months (95% CI, 13.5-28.5 months) and 12.2 months (95% CI, 8.7-19.8 months), respectively. Higher efficacy results in our retrospective analysis for patients with intermediate risk could be explained by differences in study design and patient population.\u003c/p\u003e\n\u003cp\u003eIn our real-world mRCC patient\u0026rsquo;s population, the median OS for patients with favorable risk was 68.0 months (95% CI, 29.7-106.3 months). OS results for the same patient\u0026rsquo;s population in ADONIS trial [12] was similar (67.4 months (95% CI, 46.3-102 months) and comparable to OS data presented by Schwab et al. (72.0 months), however in retrospective analysis done by Schwab et al. mRCC patients were treated not only with sunitinib but also with other TKIs, mTOR inhibitors [13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMajority of patients (94%) in our study had prior cytoreductive nephrectomy (CN) and it is well known that CN may provide an OS benefit in selected mRCC patient\u0026rsquo;s population [14,15]. Metastasis volume, count and site are important assessing response to the treatment [16]. \u0026nbsp;Our data shows that patients diagnosed with more than 3 metastases had lower OS compared to patients with 3 and less metastases (44.0 months versus 70.0 months). It should be mentioned that metastasectomy is associated with improved oncologic outcomes and plays an important role in patient survival. Six studies reported a significantly longer median OS or cancer-specific survival (CSS) following complete metastasectomy (the median value for OS or CSS was 40.75 months, range 23\u0026ndash;122 months) compared with incomplete and/or no metastasectomy (the median value for OS or CSS was 14.8 months, range 8.4\u0026ndash;55.5 months) [17-22]. Three studies reported the complex treatment of RCC metastases in the lung [23], liver [24] and pancreas [25], respectively. The lung metastases study reported a significantly higher median OS for metastasectomy vs. medical therapy (for both targeted therapy and immunotherapy) [23-25]. Similarly, the liver and pancreas metastases study reported a significantly higher median OS and five-year OS for metastasectomy vs. no metastasectomy [23,25]. In our cohort, 30% of patients underwent metastasectomy and this factor possibly had a positive impact on OS.\u003c/p\u003e\n\u003cp\u003eUndoubtedly, an appropriate systemic treatment choice strategy results in prolonged patient survival [26, 27]. According to our retrospective data, second-line therapy after sunitinib was mainly axitinib (48 %) and other treatment modalities (cabozantinib, nivolumab). \u0026nbsp;One of explanations for the prolonged OS in our patient\u0026rsquo;s population within each risk group in comparison with pivotal phase III sunitinib trial [28], might be the benefit obtained from the second-line treatment with the newer systemic therapies such as axitinib, cabozantinib, nivolumab.\u003c/p\u003e\n\u003cp\u003eNowadays, immunotherapy-based drug combinations, such as IO-TKI and IO-IO regimens, are widely used and proved their benefit and significant clinical efficacy [29]. The phase III trials as CheckMate 214 (nivolumab plus ipilimumab), CheckMate 9ER (Nivolumab plus cabozantinib), KEYNOTE-426 (Pembrolizumab plus axitinib), IMmotion151 (Atezolizumab plus bevacizumab) showed a superiority of over sunitinib with OS up to 47 months, focused on the IMDC intermediate- and poor-risk population [30]. The median OS with nivolumab plus ipilimumab was 74 months for favorable- risk patients [31]. Combinations of immunotherapies and antiangiogenetic agents have improved patient outcomes, but sunitinib still shows sufficient efficacy and can be used especially in countries where novel combinations not reimbursed yet.\u003c/p\u003e\n\u003cp\u003eLimitations of our study include the retrospective data analysis, relatively small patient\u0026rsquo;s cohort, not presented treatment related adverse events. However, such everyday clinical practice-based data provide further rationale on the use of sunitinib for mRCC with low to intermediate risk criteria.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEveryday clinical practice-based data shows sufficient efficacy of sunitinib in mRCC patients with favorable and intermediate risk according to IMDC. Favorable clinical responses can be achieved using sunitinib as a first-line treatment, especially in countries where novel combinations such as nivolumab/cabozantinib, pembrolizumab/axitinib, nivolumab/ipilimumab are not reimbursed yet. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe retrospective analysis of available patient data was performed in accordance with the declaration of Helsinki and approved by the institutional ethics committee (Vilnius University Faculty of Medicine, ethics protocol number 2019/2˗1074˗586).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\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\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to privacy legislation but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econtribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAZ: data collection, literature review and manuscript preparation; Others: statistical analysis, revising manuscript critically for important intellectual content, have made substantial contributions to conception and design. All authors are supported by the Vilnius University. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the contributions of all the oncologist and urologist of the National Cancer Institute, for the care and treatment of patients included in our study cohort.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003einformation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003ePatard JJ, Leray E, Rodriguez A, NathalieRioux-Leclercq N, Guill\u0026eacute;a F, Lobel B. Correlation between symptom graduation, tumor characteristics and survival in renal cell carcinoma. 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New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy. J Hematol Oncol. 2017;10(1):38. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13045-016-0374-y\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMotzer RJ, Hutson ThE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Georg A, et al. Overall Survival and Updated Results for Sunitinib Compared with Interferon Alfa in Patients with Metastatic Renal Cell Carcinoma. J Clin Oncol August. 2009;01(22):3584\u0026ndash;90. 27.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eQuhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B, Schuettfort VM, Laukhtina E, Egawa Sh., Fajkovic H, et al. First-line Immunotherapy-based Combinations for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis. European Urology Oncology. Volume\u0026nbsp;4, Issue 5, October 2021, Pages 755\u0026ndash;765.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLjungberg B, Albiges L, Bedke J, Bex A, Capitanio U, Giles RH, Hora M, Klatte T, Lam T, Marconi L, et al. Renal Cell Carcinoma. EAU 2022 guidelines.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMotzer RJ, Tannir NM, McDermott DF, Burotto M, Choueiri TK, Hammers HJ, Plimack ER, Porta CG, George S, Powles TB, et al. Conditional survival and 5-year follow-up in CheckMate 214: First-line nivolumab + ipilimumab (N + I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC). Ann Oncol. 2021;32:68.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Renal cell carcinoma, metastasis, sunitinib, risk groups,","lastPublishedDoi":"10.21203/rs.3.rs-2032562/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2032562/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction and Objectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSunitinib, according to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommendations, is one of the recommended regimens for favorable and intermediate risk metastatic renal cell carcinoma (mRCC) patients. Our objective was to evaluate sunitinib efficacy as a first-line treatment for mRCC patients with favorable / intermediate prognostic risk in a real-world setting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with diagnosed mRCC and confirmed as appropriate candidates for the first-line systemic treatment were included in the retrospective study. The prognostic risk was evaluated according to the model of International Metastatic RCC Database Consortium (IMDC). Patients received sunitinib as a first-line treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 94 patients were enrolled from 2019 to the 2020 year. 67 patients were included for the detailed analysis. The median age at diagnosis was 62 years. Majority of patients had clear cell renal carcinoma with prior nephrectomy. Half of patients had more than 3 metastatic sites. Metastasectomy was performed for one third of the patients. Median progression-free survival (PFS) was 23.4 (95% CI: 17.3-29.5), and median overall survival (OS) was 66 months (95% CI: 44.9-87.1). The age over 60 years was significant negative predictor for PFS and OS. Regarding IMDC model for disease risk prediction, the number of two risk factors in the intermediate risk group was a significant predictor for a shorter response to the first-line therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn everyday clinical practice, sunitinib is an effective systemic therapy for favorable/intermediate risk groups mRCC patients. This tyrosine kinase inhibitor (TKI) can be used as a first-line treatment in this group of patients, especially in countries where novel systemic treatment modalities are not available yet.\u003c/p\u003e","manuscriptTitle":"Sunitinib in patients with favorable and intermediate risk metastatic renal cell carcinoma – Lithuanian National Cancer Institute experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-23 14:48:10","doi":"10.21203/rs.3.rs-2032562/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"35559103-57e5-4ef3-9181-b35777b12203","owner":[],"postedDate":"September 23rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-16T10:29:34+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-23 14:48:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2032562","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2032562","identity":"rs-2032562","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}