IKCS 2022: Efficacy and Safety of Nivolumab plus Ipilimumab Versus Sunitinib for First-Line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma in the Phase 3 CheckMate 214 Trial with Extended 5-Year Minimum Follow-Up

(UroToday.com) The 2022 IKCS North American annual meeting featured a presentation by Dr. Nazir Tannir discussing efficacy and safety of nivolumab plus ipilimumab versus sunitinib for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (RCC) in the phase 3 CheckMate 214 trial1 with extended 5-year minimum follow-up. Sarcomatoid RCC is an aggressive histologic growth pattern in RCC with a poor prognosis and limited therapeutic options. About 5% of patients with RCC have sarcomatoid features, including up to 20% of patients with advanced disease. First-line nivolumab + ipilimumab provided efficacy benefits over sunitinib in patients with sarcomatoid RCC and intermediate/poor-risk disease at 42 months follow-up. At the 2022 IKCS North American meeting, Dr. Tannir reported an exploratory post hoc analysis of nivolumab + ipilimumab vs sunitinib in patients with intermediate/poor-risk and sarcomatoid RCC with long-term follow-up of 5 years.

Patients with clear cell advanced RCC were randomized 1:1 to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks × 4, then nivolumab 3 mg/kg every 2 weeks vs sunitinib 50 mg once daily (4 weeks; 6-week cycles). Patients with sarcomatoid RCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology.

Outcomes in patients with sarcomatoid RCC were not prespecified. Endpoints in patients with sarcomatoid RCC and IMDC intermediate/poor risk included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Outcomes were also assessed per baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes used descriptive statistics.

Of 1,096 randomized patients in CheckMate 214 [1], 139 intermediate/poor-risk patients with sarcomatoid RCC were identified (nivolumab + ipilimumab, n = 74; sunitinib, n = 65). Of all treated patients, 9 of 73 (12%) in the nivolumab + ipilimumab arm vs zero of 65 in the sunitinib arm remained on treatment, with the primary reason for discontinuation was disease progression (nivolumab + ipilimumab, 37%; sunitinib, 71%). OS continued to favor nivolumab + ipilimumab vs sunitinib (48.6 months vs 14.2 months; HR 0.46, 95% CI 0.29–0.71):


PFS benefit with nivolumab + ipilimumab vs sunitinib was similarly maintained (26.5 months vs 5.5 months; HR 0.50, 95% CI 0.32–0.80)


ORR was also higher (61% vs 23%; p < 0.0001) for nivolumab + ipilimumab vs sunitinib:


Additionally, median duration of response was longer (not reached vs 25 months), and more patients had complete responses (23% vs 6%) with nivolumab + ipilimumab vs sunitinib, respectively. Efficacy was better with nivolumab + ipilimumab vs sunitinib regardless of PD-L1 expression, yet the degree of OS, PFS, and ORR benefits with nivolumab + ipilimumab was greater for patients with PD-L1 ≥ 1%. No new safety signals emerged in either arm, with treatment-related adverse events grade 3/4 occurring in 49% of patients receiving nivolumab + ipilimumab and 45% for sunitinib.

Dr. Tannir concluded his presentation of long-term follow-up of efficacy and safety results of nivolumab + ipilimumab versus sunitinib for first-line treatment of patients with advanced sarcomatoid RCC in the phase 3 CheckMate 214 trial with the following take-home messages:

  • With long-term follow-up, nivolumab + ipilimumab showed clinically meaningful benefits in long-term OS, PFS, and the frequency and depth of response vs sunitinib in previously untreated patients with sarcomatoid RCC and intermediate/poor-risk disease
  • No new safety signals were identified with nivolumab + ipilimumab or sunitinib, and the safety profile observed was consistent with the trial population as a whole
  • This supports nivolumab + ipilimumab as a preferred first-line therapy in this population

Presented by: Nazir Tannir, MD, University of Texas MD Anderson Cancer Center, Houston, TX

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 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA  


  1. 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.