Ramucirumab Plus Erlotinib vs. Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated Non-small Cell Lung Cancer: RELAY Japanese Subset

ABSTRACT Introduction The phase 3 RELAY global study (NCT02411448) showed significant improvement in progression-free survival (PFS) with ramucirumab plus erlotinib (RAM+ERL) compared with placebo plus erlotinib (PL+ERL) in untreated EGFR-mutated metastatic non-small cell lung cancer. This prespecified analysis evaluates efficacy, safety, and post-progression EGFR T790M rates of RELAY patients enrolled in Japan. Methods Patients were randomized (1:1) to oral erlotinib (150 mg/day) plus intravenous ramucirumab (10 mg/kg) or placebo every 2 weeks. Endpoints included: PFS (primary); safety (secondary); and biomarker analyses (exploratory). Plasma samples collected at baseline and post-study treatment discontinuation were assessed for EGFR T790M mutations by next-generation sequencing. Results The Japanese subset included 211/449 (47.0%) RELAY patients (RAM+ERL, n=106; PL+ERL, n=105). Median PFS was 19.4 vs. 11.2 months for RAM+ERL vs. PL+ERL treatment (hazard ratio [HR]: 0.610; 95% confidence interval [CI]: 0.431-0.864) in the Japanese intent-to-treat population, 16.6 vs. 12.5 months (HR: 0.701 [0.424-1.159]) in the EGFR exon 19 deletion subgroup, and 19.4 vs. 10.9 months (HR: 0.514 [0.317-0.835]) in the EGFR exon 21 L858R subgroup, respectively. Grade ≥3 adverse events with RAM+ERL included hypertension (24.8%, all grade 3) and dermatitis acneiform (23.8%). Post-progression treatment-emergent T790M rates were similar between arms (RAM+ERL: 47%, 9/19 patients; PL+ERL: 50%, 20/40 patients). Conclusions Clinically meaningful efficacy was observed with RAM+ERL vs. PL+ERL in the RELAY Japanese subset, with no new safety concerns. Post-progression T790M rates were similar across treatment arms, indicating that the addition of ramucirumab did not affect the erlotinib-associated EGFR T790M rates at disease progression.