Updated CheckMate 214 analysis confirms nivolumab–ipilimumab RCC benefit
medwireNews: CheckMate 214 data presented at the 2020 Genitourinary Cancers Symposium show the continued benefit of combination treatment with nivolumab plus ipilimumab over sunitinib in individuals with treatment-naïve advanced renal cell carcinoma (RCC).
Reporting on a median 49 months of follow-up, the presenting author Nizar Tannir (The University of Texas MD Anderson Cancer Center, Houston, USA) highlighted to the audience in San Francisco, California, USA, that “these results represent the longest follow-up in a phase 3 trial of a checkpoint inhibitor combination for first-line treatment of patients with advanced RCC.”
The phase 3 trial included 847 patients with untreated advanced RCC who were randomly assigned to receive either nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks, followed by nivolumab at the same dose every 2 weeks, or sunitinib 50 mg/day for 4 weeks of each 6-week cycle.
The previously reported primary analysis at a median of 25.2 months and a follow-up analysis at a median of 32.4 months both demonstrated significant improvements with nivolumab–ipilimumab versus sunitinib in all three co-primary endpoints of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in the primary efficacy population comprising IMDC intermediate- and poor-risk patients. The findings were similar in the intention-to-treat (ITT) population that also included favorable-risk patients, except that the difference in PFS was not significant in the primary analysis.
In the latest update, the combination immunotherapy continued to be associated with a significant OS and PFS benefit relative to sunitinib in the primary efficacy population, with median times of 47.0 versus 26.6 months and 12.0 versus 8.3 months, respectively, and 42-month rates of 52% versus 39% and 35% versus 19%, respectively.
This was also the case for response, with ORRs of 42% and 26% (10 vs 1% complete responses) for nivolumab–ipilimumab and sunitinib, respectively, while the corresponding median durations of response were unreached and 19.7 months.
Once again, the results were similar in the ITT population, except for PFS, where the between-group difference did not reach statistical significance. But the presenter highlighted that “PFS curves plateaued after 30 months at [around] 35%” with nivolumab plus ipilimumab in both the primary efficacy and ITT populations.
Tannir also presented an exploratory efficacy analysis restricted to the 249 favorable-risk participants, but there was no significant difference between the groups with regard to OS, and both PFS and ORR appeared to be significantly poorer with the combination than sunitinib, with median PFS times of 17.8 versus 27.7 months and ORRs of 29% versus 54%.
The presenter pointed out, however, that the complete response rate remained higher with combination immunotherapy than sunitinib even in this subgroup, at 13% and 6%, respectively.
In terms of the adverse event (AE) profile of nivolumab plus ipilimumab, “incidence of treatment-related AEs, treatment-related select immune-related AEs, and corticosteroid use declined over time,” commented Tannir.
“And importantly, there were no new safety signals” with the longer follow-up, he concluded.
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA