Background The phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival (PFS) with first-line atezolizumab (A) vs placebo (P) combined with vemurafenib (V) + cobimetinib (C) in patients with BRAF^V600 mutation–positive advanced melanoma (15.1 vs 10.6 months; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.63–0.97; P=0.0249). Objective response has been associated with increased survival with chemotherapy and targeted therapies, but it is unclear whether the association holds for immunotherapy. In this exploratory analysis, we evaluated the impact of response on survival outcomes in patients treated with A+V+C or P+V+C in the IMspire150 study.

Methods 514 patients were randomized 1:1 to A+V+C (n=256) or P+V+C (n=258). Patients received V+C in cycle 1; A or P was added on days 1+15 from cycle 2 onward. The primary endpoints for this exploratory analysis were PFS and overall survival (OS), estimated using the Kaplan-Meier method. Outcomes were analyzed by investigator-assessed best overall response (BOR) per RECIST v1.1 (complete response [CR] vs partial response [PR] vs stable disease [SD]).

Results Median follow-up was 18.9 mo. In the A+V+C arm, BOR was CR (n=41), PR (n=129), and SD (n=58); in the P+V+C arm, BOR was CR (n=46), PR (n=122), and SD (n=58). An imbalance in baseline prognostic factors (eg, lactate dehydrogenase, tumor burden measures) was noted across response categories in both treatment arms, with favorable factors more prevalent in patients with CR and unfavorable factors more prevalent in patients with PR/SD. Improvement in PFS and OS was observed with A+V+C vs P+V+C in patients with PR, with 2-year PFS rates of 42.1% vs 24.6% and 2-year OS rates of 69.1% vs 56.1% with A+V+C vs P+V+C (table 1). In patients with CR, median PFS and OS were not yet reached in either arm, with 2-year PFS rates of 64.6% vs 59.8% and 2-year OS rates of 82.6% vs 82.8% with A+V+C vs P+V+C. PFS and OS outcomes were poor in both treatment arms in patients with SD, with 2-year PFS rates of 10.7% vs not estimable (NE) and 2-year OS rates of 36.6% vs 29.3% with A+V+C vs P+V+C.

Conclusions PFS and OS improvement was observed for A+V+C vs P+V+C for patients who achieved PR. CR is associated with improved PFS and OS with both A+V+C and P+V+C. Further follow-up is required to determine the impact of A+C+V vs P+C+V on survival outcomes.

Trial Registration ClinicalTrials. gov, NCT02908672