(UroToday.com) The 2022 ASCO annual meeting featured a session on kidney and bladder cancer, including a presentation by Dr. Charlene Mantia discussing prognostic factors for patients with advanced renal cell carcinoma (RCC) in the era of first-line treatment with immune checkpoint inhibitors. The most commonly used prognostic models in advanced RCC, the Memorial Sloan-Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, were developed when cytokines and VEGF targeted monotherapies were standard of care:
Advanced RCC first-line treatment now includes combination therapy with two ICIs or ICI + VEGF receptor inhibitor. Re-evaluation of the MSKCC and IMDC prognostic models in the era of ICI therapy and identification of additional prognostic factors are overdue.
Data from 1,052 patients with advanced RCC treated on the CheckMate-214 clinical trial [1] with first-line nivolumab + ipilimumab or sunitinib were analyzed retrospectively at median follow-up 5 years. For each treatment group, multivariable Cox model hazard ratios were compared to the published MSKCC and IMDC model hazard ratios. Discrimination (c index) was assessed based upon the continuous scores obtained as the weighted combination of regression parameters from the published MSKCC & IMDC models.
The following table summarizes the distributions of the IMDC prognostic factors and risk categories in the IMDC model development cohort and CheckMate 214 trial cohort, which expectedly differs as cohorts of patients treated with VEGFR TKIs in clinical practice and those patients eligible for clinical trial:
When re-fitting multivariable Cox models in each CheckMate 214 treatment group using the six IMDC prognostic factors, KPS < 80% remained highly prognostic in both treatment groups (hazard ratios > 2.5). With the exception of high calcium, the other factors of time from diagnosis to treatment < 1 year, hemoglobin < lower limit of normal (LLN), neutrophils > upper limit of normal (ULN), platelets > ULN and LDH > 1.5 x ULN consistently retained prognostic value for sunitinib (hazard ratios ≥ published model hazard ratios) but had diminished prognostic value for nivolumab + ipilimumab (each hazard ratio < published model hazard ratio). High calcium had diminished prognostic value for sunitinib and retained prognostic value for nivolumab + ipilimumab:
The c-indices for discrimination were 0.61 and 0.64 for the MSKCC model in the nivolumab + ipilimumab and sunitinib treatment groups, respectively, and were 0.63 and 0.67 for the IMDC model in the nivolumab + ipilimumab and sunitinib treatment groups compared to reported IMDC c-index of 0.73.
Dr. Mantia concluded her presentation discussing prognostic factors for patients with advanced RCC in the era of first-line treatment with immune checkpoint inhibitors with the following take-home messages:
- Strength of the relationships of some prognostic factors in the IMDC model, and of their combination as a prognostic model score, is reduced among patients receiving first-line treatment with combination immune checkpoint inhibitors as compared with VEGFR-targeted TKI
- Longer follow-up and survival since initiation of first-line therapy contribute to the diminution of prognostic relationships, as observed in both treatment groups, possibly related to subsequent checkpoint inhibitor administration
- Different patterns observed with nivolumab + ipilimumab than sunitinib may also reflect durability of anti-tumor activity of ICI-based combination versus VEGFR blockade
- Evaluation of additional prognostic factors and development of new risk scores are needed in the era of ICIs and improved OS, work which is ongoing
Presented by: Charlene Mantia, MD, Dana-Farber Cancer Institute, Boston, MA
Co-Authors: Opeyemi Jegede, Meredith M. Regan, Michael B. Atkins, David F. McDermott
Affiliations: Dana Farber Cancer Institute, Boston, MA, Dana-Farber Cancer Institute and International Breast Cancer Study Group, Boston, MA, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.
References:
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carinoma. N Engl J Med 2018;378(14):1277-1290.