Charlene M Mantia, Opeyemi A Jegede, David F McDermott, Daniel Y C Heng, Wanling Xie, Toni K Choueiri, Michael B Atkins, Meredith M Regan
{"title":"Long-Term Performance of Prognostic Models for Advanced Renal Cell Carcinoma in the Era of Improved Survival With Immune Checkpoint Inhibitors.","authors":"Charlene M Mantia, Opeyemi A Jegede, David F McDermott, Daniel Y C Heng, Wanling Xie, Toni K Choueiri, Michael B Atkins, Meredith M Regan","doi":"10.1200/OP-25-00089","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>In the era of prolonged survival for advanced renal cell carcinoma (aRCC) with standard-of-care first-line therapy now including immune checkpoint inhibitor, re-evaluation of the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium (IMDC) prognostic models is overdue.</p><p><strong>Methods: </strong>Data from 1,052 patients with aRCC treated on the CheckMate-214 phase III randomized trial with first-line nivolumab + ipilimumab or sunitinib were analyzed after minimum 5 years of follow-up. The end point was overall survival (OS). To investigate long-term prognostication with each treatment approach, model performance based upon continuous risk score was assessed in a time-dependent manner of increasing 6-month intervals and globally over full follow-up, using discrimination concordance (c)-indices.</p><p><strong>Results: </strong>With time-dependent assessment, the IMDC and MSKCC models maintained their performance over approximately 2 years from sunitinib initiation (c ≥0.69 through 18-24 months); thereafter, the models' performances with long-term OS attenuated. Over full follow-up, the models' discrimination was c = 0.66 (95% CI, 0.658 to 0.664) and c = 0.64 (95% CI, 0.640 to 0.645), respectively, for the sunitinib group. After nivolumab + ipilimumab initiation, the IMDC and MSKCC models' global discrimination was c = 0.63 (95% CI, 0.628 to 0.634) and c = 0.61 (95% CI, 0.607 to 0.614), respectively. The models' performances were attenuated in the short term (c ranging 0.64-0.69 through 18-24 months) and the long term.</p><p><strong>Conclusion: </strong>This retrospective analysis of the CheckMate-214 trial, in which nivolumab + ipilimumab improved survival versus sunitinib with 48% and 37% of patients, respectively, surviving beyond 5 years, confirmed the strength of the models' prognostication for the early years after first-line sunitinib initiation continuing to stratify three prognostic categories, but also diminished discrimination among long-term survivors and with initiation of nivolumab + ipilimumab. As novel treatments are developed and patients with aRCC live longer, new models to estimate long-term prognosis are needed.</p>","PeriodicalId":14612,"journal":{"name":"JCO oncology practice","volume":" ","pages":"OP2500089"},"PeriodicalIF":4.6000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262164/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO oncology practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/OP-25-00089","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: In the era of prolonged survival for advanced renal cell carcinoma (aRCC) with standard-of-care first-line therapy now including immune checkpoint inhibitor, re-evaluation of the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium (IMDC) prognostic models is overdue.
Methods: Data from 1,052 patients with aRCC treated on the CheckMate-214 phase III randomized trial with first-line nivolumab + ipilimumab or sunitinib were analyzed after minimum 5 years of follow-up. The end point was overall survival (OS). To investigate long-term prognostication with each treatment approach, model performance based upon continuous risk score was assessed in a time-dependent manner of increasing 6-month intervals and globally over full follow-up, using discrimination concordance (c)-indices.
Results: With time-dependent assessment, the IMDC and MSKCC models maintained their performance over approximately 2 years from sunitinib initiation (c ≥0.69 through 18-24 months); thereafter, the models' performances with long-term OS attenuated. Over full follow-up, the models' discrimination was c = 0.66 (95% CI, 0.658 to 0.664) and c = 0.64 (95% CI, 0.640 to 0.645), respectively, for the sunitinib group. After nivolumab + ipilimumab initiation, the IMDC and MSKCC models' global discrimination was c = 0.63 (95% CI, 0.628 to 0.634) and c = 0.61 (95% CI, 0.607 to 0.614), respectively. The models' performances were attenuated in the short term (c ranging 0.64-0.69 through 18-24 months) and the long term.
Conclusion: This retrospective analysis of the CheckMate-214 trial, in which nivolumab + ipilimumab improved survival versus sunitinib with 48% and 37% of patients, respectively, surviving beyond 5 years, confirmed the strength of the models' prognostication for the early years after first-line sunitinib initiation continuing to stratify three prognostic categories, but also diminished discrimination among long-term survivors and with initiation of nivolumab + ipilimumab. As novel treatments are developed and patients with aRCC live longer, new models to estimate long-term prognosis are needed.