CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

4513 Background: Patients (pts) with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognosis and suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus ipilimumab (N+I) demonstrated superior objective response rate (ORR) and overall survival (OS) vs sunitinib (S) in previously untreated pts with International Metastatic RCC Database Consortium (IMDC) intermediate/poor (I/P)-risk, clear-cell, advanced RCC in the phase 3 CheckMate 214 trial. Methods: We performed a post-hoc exploratory analysis of N+I vs S in CheckMate 214 sRCC pts. The presence of sarcomatoid features was assessed by keyword search for “sarcomatoid” in pts with available local pathology reports accompanying pretreatment tumor samples. Results: 842 (77%) of 1096 intention-to-treat pts had local pathology reports available, including 112 randomized pts with I/P-risk sRCC (N+I, n = 60; S, n = 52). Baseline characteristics of sRCC pts were balanced between arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S arms had tumor PD-L1 expression ≥1% at baseline, which was higher than in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed at a minimum follow-up of 30 months, confirmed ORR and complete response rate per investigator (RECIST v1.1), OS, and progression-free survival (PFS) per investigator were improved with N+I vs S in I/P-risk pts with sRCC (Table). No new safety signals were seen in sRCC pts. Conclusions: In this post-hoc descriptive subgroup analysis of CheckMate 214, N+I demonstrated promising efficacy and prolonged survival vs S, with consistent safety, in previously untreated, I/P-risk, advanced clear-cell RCC with sarcomatoid features. Prospective studies of N+I that include pts with sRCC are ongoing. Clinical trial information: NCT02231749. Table: see text