In the first long-term conditional survival analyses of the CheckMate 214 trial, nivolumab plus ipilimumab yielded durable survival and response benefits relative to sunitinib in patients with advanced renal cell carcinoma (aRCC). These findings were presented at the International Kidney Cancer Symposium (IKCS) 2021.
Investigators presented updated efficacy and safety outcomes and conditional survival outcomes from CheckMate 214 (ClinicalTrials.gov Identifier: NCT02231749) with 5 years minimum follow-up duration (median, 67.7 months), representing the longest phase 3 follow up reported for a checkpoint inhibitor combination therapy in aRCC.
Patients with clear cell aRCC were randomly assigned (1:1) to receive nivolumab plus ipilimumab (3 and 1 mg/kg) every 3 weeks for 4 doses followed by nivolumab (3 mg/kg) every 2 weeks or sunitinib (50 mg) once daily for 4 weeks (6 week cycles).
The investigators evaluated overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in intermediate/poor-risk (I/P), intent-to-treat (ITT), and favorable-risk (FAV) populations as well as conditional survival (defined as the probability of remaining alive, progression-free, or in response 2 years beyond landmark timepoints of 2 and 3 years).
A total of 1096 patients were randomly assigned to receive nivolumab plus ipilimumab or sunitinib (ITT, 550 and 546; I/P, 415 and 422; FAV, 125 and 124). Key baseline characteristics were well balanced across treatment arms.
At 5 years of follow up in the ITT population, 6% of patients in the nivolumab plus ipilimumab arm and 2% of patients in the sunitinib arm remained on therapy. Median duration of therapy was 7.9 months (interquartile range, 2.1-21.8) in the nivolumab plus ipilimumab arm and 7.8 months (interquartile range, 3.5-19.6) in the sunitinib arm. Subsequent systemic therapy was received by 55% of patients in the nivolumab plus ipilimumab arm and 68% of patients in the sunitinib arm.
Higher ORR, 5-year median (m) OS and mPFS were maintained with nivolumab plus ipilimumab compared with sunitinib in the ITT (ORR, 39% vs 32%; mOS, 48% vs 37%; mPFS, 30% vs 14%) and I/P-risk populations (ORR, 42% vs 27%; mOS, 43% vs 31%; mPFS, 31% vs 11%). Most outcomes in the FAV-risk population were similar between the treatment arms (ORR, 30% vs 52%; mOS, 63% vs 55%; mPFS, 26% vs 21%). More patients also achieved a complete response (CR) with nivolumab plus ipilimumab compared with sunitinib, regardless of risk (ITT, 12% vs 3%; I/P-risk, 11% vs 2%; FAV-risk, 13% vs 7%).
The probability of remaining alive, progression-free, or in response for an additional 2 years from randomization to landmark year 3 increased for the ITT (71% to 81%) and I/P-risk (66% to 79%) populations, while it remained 85% in the FAV-risk population. Regardless of risk population, nivolumab plus ipilimumab consistently resulted in conditional OS beyond the 3-year landmark compared with sunitinib in all patients (ITT, 81% vs 72%; I/P-risk, 79% vs 72%; FAV-risk, 85% vs 72%). The probability of remaining progression free for an additional 2 years increased from time of random assignment to year 3 with nivolumab plus ipilimumab for all risk populations (ITT, 37%-89%; I/P-risk, 36%-90%; FAV-risk, 38%-85%).
The investigators found no new safety signals with the longer follow-up period.
“Taken together, these results highlight the durable clinical benefits observed with [nivolumab plus ipilimumab] versus [sunitinib] in patients with aRCC after 5 years of follow-up and show that most patients alive or in response at the 3-year landmark will remain alive or in response at 5 years with [nivolumab plus ipilimumab],” concluded the investigators.
Disclosure: This research was supported by Bristol Myers Squibb. Please see the original reference for a full list of authors’ disclosures.
Hammers HJ, Motzer RJ, Tannir NM, et al. Conditional survival and 5-year follow-up in CheckMate 214: first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in advanced renal cell carcinoma (aRCC). Presented at IKCS 2021; November 5-6, 2021. Abstract E39.