Time to central nervous system (CNS) metastases (mets) with atezolizumab (A) or placebo (P) combined with cobimetinib (C) + vemurafenib (V) in the phase III IMspire150 study.

Abstract

10023 Background: The phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival with first-line combination treatment with A+C+V vs P+C+V in patients (pts) with previously untreated BRAFV600 mutation–positive advanced melanoma. Here we report incidence and time to development of CNS mets with A+C+V vs P+C+V in the IMspire150 study. Methods: Eligible pts were randomized 1:1 to receive A+C+V or P+C+V. A or P were given on day 1 and 15 of each 28-day cycle after an initial cycle of C+V. Incidence and time to development of CNS mets were evaluated in pts with no history of CNS mets at baseline confirmed by magnetic resonance imaging/computed tomography (MRI/CT). On study MRI/CT assessments were performed as clinically indicated. Time-to-event outcomes were estimated using the Kaplan-Meier method and competing risks analysis. Sensitivity analyses were conducted using landmark analysis at time of initiation of A or P. Results: 514 pts were randomized to receive A+C+V (n = 256) or P+C+V (n = 258); 244 and 247 pts, respectively, had no history of CNS mets at baseline. After a median follow-up of 18.9 months, CNS mets had developed in 52/244 pts (21%) in the A+C+V arm and 62/247 pts (25%) in the P+C+V arm. In both arms, pts with CNS mets were more likely to have other known unfavorable prognostic factors: elevated LDH, presence of liver mets, and/or higher tumor burden. Cumulative incidence of CNS mets as first site of progressive disease with A+C+V vs P+C+V was 8% vs 9%, 16% vs 19%, 20% vs 24%, and 23% vs 26% at 6, 12, 18, and 24 months, respectively (hazard ratio [HR] 0.87; 95% CI 0.60-1.26). Estimated CNS mets-free survival rates for A+C+V vs P+C+V were 91% vs 90%, 81% vs 75%, 74% vs 66%, and 69% vs 62% at 6, 12, 18, and 24 months, respectively, with a trend for improved CNS mets-free survival with A+C+V (HR 0.79; 95% CI 0.55-1.14). Results of landmark analyses for CNS mets-free survival and cumulative incidence of CNS mets were similar to those in the overall analysis. Conclusions: The addition of anti–programmed death-ligand 1 to C+V is associated with numerically lower rates of interval development of CNS mets, consistent with the overall benefit observed for A+C+V in the study. This finding requires further follow-up to fully assess the magnitude of benefit of A+C+V on CNS mets-free survival. Clinical trial information: NCT02908672.