Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma.

Background: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months minimum follow-up in the phase 3 CheckMate 214 trial. In this exploratory post hoc analysis, we report clinical efficacy of NIVO+IPI in sRCC after a minimum follow-up of 5 years.

Methods: In CheckMate 214, patients with clear cell advanced RCC were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks (four doses), then NIVO 3 mg/kg every 2 weeks versus SUN 50 mg once daily (4 weeks; 6-week cycles). Randomized patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Overall survival (OS), as well as progression-free survival (PFS) and objective response rate (ORR) per independent radiology review using Response Evaluation Criteria in Solid Tumors V.1.1, were evaluated in all International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk sRCC patients and by baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes are reported using descriptive statistics.

Results: In total, 139 patients with intermediate/poor-risk sRCC were identified (NIVO+IPI, n=74; SUN, n=65). At 5 years minimum follow-up, more patients remained on treatment with NIVO+IPI versus SUN (12% vs zero). Efficacy benefits with NIVO+IPI versus SUN were maintained with median OS of 48.6 vs 14.2 months (HR 0.46), median PFS of 26.5 vs 5.5 months (HR 0.50), and ORR 60.8% vs 23.1%. In addition, median duration of response was longer (not reached vs 25.1 months), and more patients had complete responses (23.0% vs 6.2%) with NIVO+IPI versus SUN, respectively. Efficacy was better with NIVO+IPI versus SUN regardless of tumor PD-L1 expression, but the magnitude of OS, PFS, and ORR benefits with NIVO+IPI was greater for sRCC patients with tumor PD-L1 ≥1%. No new safety signals emerged in either arm with longer follow-up.

Conclusions: Among patients with intermediate/poor-risk sRCC, NIVO+IPI maintained long-term survival benefits and demonstrated durable and deep responses over SUN at minimum follow-up of 5 years, supporting NIVO+IPI as a preferred first-line therapy in this population.

Trial Registration Number: NCT02231749.