TY - JOUR
T1 - Long-Term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma
AU - Rini, Brian I.
AU - Signoretti, Sabina
AU - Choueiri, Toni K.
AU - McDermott, David F.
AU - Motzer, Robert J.
AU - George, Saby
AU - Powles, Thomas
AU - Donskov, Frede
AU - Tykodi, Scott S.
AU - Pal, Sumanta K.
AU - Gupta, Saurabh
AU - Lee, Chung Wei
AU - Jiang, Ruiyun
AU - Tannir, Nizar M.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2022.
PY - 2022/12/22
Y1 - 2022/12/22
N2 - 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.
AB - 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.
KW - CTLA-4 Antigen
KW - Drug Therapy, Combination
KW - Immunotherapy
KW - Programmed Cell Death 1 Receptor
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U2 - 10.1136/jitc-2022-005445
DO - 10.1136/jitc-2022-005445
M3 - Article
C2 - 36549781
AN - SCOPUS:85144514925
SN - 2051-1426
VL - 10
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 12
M1 - e005445
ER -