Abstract 3639: Matching-adjusted indirect comparison of nivolumab + ipilimumab and BRAF+MEK inhibitors for the treatment of BRAF-mutant treatment-naive advanced melanoma
Authors: Atkins Michael B. , McDermott David , Tarhini Ahmad , Rael Michael , Gupte-Singh Komal , O'Brien Elliot , Ritchings Corey , Rao Sumati 
Published: August 2018

OBJECTIVES: Assess the relative overall survival (OS) and progression-free survival (PFS) of nivolumab + ipilimumab (NIVO+IPI) versus dabrafenib + trametinib (DAB+TRAM) and vemurafenib + cobimetinib (VEM+COBI) in treatment-naive patients with BRAF-mutant advanced melanoma. METHODS: In the absence of a direct head-to-head comparison, matching-adjusted indirect treatment comparisons (MAIC) were conducted using patient-level data for NIVO+IPI patients with BRAF-mutant tumors from the CheckMate 067 and 069 trials and published summary level results from BRAF+MEK pivotal trials (COMBI-d, COMBI-v, and coBRIM). NIVO+IPI baseline characteristics were matched to the DAB+TRAM or VEM+COBI patient characteristics by reweighting the NIVO+IPI patients by their odds of enrollment in the studies. Additional potential biases such as use of subsequent therapy were not controlled for. Cox proportional hazard models were fit to the weighted OS and PFS data for NIVO+IPI and virtual event and censor times derived from the published DAB+TRAM or VEM+COBI curves. To capture the non-proportionality observed in the OS and PFS curves, Cox models with separate hazard ratios (HRs) for &lt;12 months and ≥12 months were also fit. RESULTS: The effective sample size of the NIVO+IPI patients was 106 after matching to DAB+TRAM and 59 after matching to VEM+COBI. The overall OS Cox models showed that NIVO+IPI had superior OS with HRs (95% confidence intervals) of 0.64 (0.46, 0.89) versus DAB+TRAM and 0.56 (0.36, 0.89) versus VEM+COBI. This benefit emerged with longer follow-up. At 12 months, the OS HRs were similar for NIVO+IPI versus DAB+TRAM (1.0; 0.67, 1.49) and VEM+COBI (1.01; 0.57, 1.80). However, beyond 12 months, NIVO+IPI had a significantly greater OS benefit versus DAB+TRAM (0.33; 0.18, 0.60) and versus VEM+COBI (0.29; 0.14, 0.63). PFS results were similar with insignificant differences observed at 12 months and superior PFS for NIVO+IPI beyond 12 months; HRs for ≥12 months were 0.29 (0.14, 0.62) for NIVO+IPI versus DAB+TRAM and 0.15 (0.04, 0.54) for NIVO+IPI versus VEM+COBI. CONCLUSION: After adjusting for patient population differences, NIVO+IPI had a significant OS benefit over DAB+TRAM and VEM+COBI. For both OS and PFS, the NIVO+IPI benefit emerges after 12 months of treatment. In the future, these results can be validated by ongoing randomized trials directly comparing sequential combination approaches. Disclosure: This research was funded by Bristol-Myers Squibb.

Citation Format: Michael B. Atkins, David McDermott, Ahmad Tarhini, Michael Rael, Komal Gupte-Singh, Elliot O'Brien, Corey Ritchings, Sumati Rao. Matching-adjusted indirect comparison of nivolumab + ipilimumab and BRAF+MEK inhibitors for the treatment of BRAF-mutant treatment-naive advanced melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3639.