Tivantinib in Combination with Erlotinib versus Erlotinib Alone for EGFR-Mutant NSCLC: An Exploratory Analysis of the Phase 3 MARQUEE Study.

INTRODUCTION

This exploratory subgroup analysis of the MARQUEE study evaluated the efficacy and safety of erlotinib plus tivantinib in patients with EGFR-mutant NSCLC.

METHODS

Patients with advanced, nonsquamous, EGFR and mesenchymal-epithelial transition inhibitor-naive NSCLC previously treated with one or two lines of systemic therapy were randomized to oral erlotinib (150 mg once daily) plus tivantinib (360 mg twice daily) or to erlotinib plus placebo. The primary end point was overall survival.

RESULTS

Among 1048 patients enrolled, 109 (10.4%) had EGFR-mutant disease. Erlotinib plus tivantinib improved progression-free survival in this subpopulation; median progression-free survival was 13.0 months for erlotinib plus tivantinib (n = 56) and 7.5 months for erlotinib plus placebo (n = 53) (hazard ratio = 0.49, 95% confidence interval: 0.31-0.77). Deaths occurred in 73 patients (67%), and median overall survival was 25.5 months in the erlotinib plus tivantinib arm versus 20.3 months in the erlotinib plus placebo arm (hazard ratio = 0.68, 95% confidence interval: 0.43-1.08). Common adverse events included diarrhea, rash, and asthenia. Neutropenia and febrile neutropenia were more common with erlotinib plus tivantinib.

CONCLUSIONS

Erlotinib plus tivantinib was tolerable and showed improved efficacy over erlotinib monotherapy in previously treated EGFR-mutant NSCLC.