Multicenter phase 2 trial of first-line ramucirumab plus erlotinib for EGFR-mutant nonsquamous NSCLC with pleural effusion

Malignant pleural effusion (MPE) develops in 30% to 40% of patients with non-small cell lung cancer (NSCLC), and is generally associated with reduced response to EGFR-TKIs. The multicenter phase 2 RELAY-Effusion trial in Japan evaluated the combination of first-line ramucirumab and erlotinib for EGFR-mutant NSCLC complicated by MPE. The primary endpoint was progression-free survival (PFS). The trial included 40 patients with a median follow-up of 29.5 months. The median PFS was 12.9 months with a 12-month PFS rate of 55% among all patients (A), 14.8 months with a 12-month PFS rate of 65% among patients with exon 19 deletion (B), and 7.3 months with a 12-month PFS rate of 41.2% among patients with L858R mutation. The overall response rate was 77.5% and the disease control rate was 85.0%. The median drainage-free survival was 33.0 months. The median overall survival was 36.3 months with a 12-month OS rate of 87.5%. Treatment-related adverse events occurred in 85% of patients (grade 3 or 4 22.5%; no grade 5). The authors conclude that although the primary endpoint (PFS 14.0 months) was not met, the combination provided durable comtrol of MPE and was well tolerated.