Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up

Abstract

Background Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-to-treat (ITT) patients and safety (ITT patients). Results Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months’ minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19–1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62–2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3–4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.

Efficacy and safety of first‐line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study

“…The ORR, 1‐year PFS and 1‐year OS were similar between our study and the CheckMate 214 trial (ORR 39% vs 42%; PFS 55% vs 50%; and OS 75% vs 79%, respectively), despite the uneven distribution of age (68 years in this study vs 61 years in the trial) and the IMDC poor‐risk group (48% in the present study vs 21% in the trial) 15 . It was also consistent with the analysis of Japanese patients in CheckMate 214 with a 39% ORR (CR 6% and PR 32%) 14 …”

“…15 It was also consistent with the analysis of Japanese patients in CheckMate 214 with a 39% ORR (CR 6% and PR 32%). 14 We observed similar oncological outcomes in this study in comparison with CheckMate 214 trial despite the age and the prevalence of IMDC risk classification differences. The main reason might be the short follow-up periods and the regional bias in Japan.…”

“…Approximately 1.5-fold longer median survival time has been reported in previous studies in Japan than in North America or Europe. 14,15,[17][18][19][20][21][22] Health insurance systems and racial differences could be possible reasons. The public health insurance system for its citizens in Japan covers almost every standard treatment, including surgery, targeted therapy and immunotherapy.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] Randomized studies suggested the efficacy of first-line nivolumab plus ipilimumab in patients belonging to the intermediate-and poor-risk groups of the IMDC. [13][14][15] However, the efficacy and safety of the first-line nivolumab plus ipilimumab for mRCC patients need to be validated in actual practice, 14 and CheckMate 214 trial only enrolled a limited number of Japanese patients. Also, no predictive factors for efficacy are available for nivolumab plus ipilimumab.…”

“…The introduction of tyrosine kinase inhibitors and immunotherapies has remarkably improved the survival of mRCC patients 1–12 . Randomized studies suggested the efficacy of first‐line nivolumab plus ipilimumab in patients belonging to the intermediate‐ and poor‐risk groups of the IMDC 13–15 . However, the efficacy and safety of the first‐line nivolumab plus ipilimumab for mRCC patients need to be validated in actual practice, 14 and CheckMate 214 trial only enrolled a limited number of Japanese patients.…”