RELAY: Final Overall Survival with Erlotinib+Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC (mNSCLC)

RELAY (NCT02411448) was a Phase 3 global double-blind, placebo-controlled study. Erlotinib (ERL)+ramucirumab (RAM) demonstrated statistically significant improvement in the primary endpoint of progression-free survival (PFS) (HR 0.59 [95% CI 0.461–0.760, p<0.0001, mPFS 19.4 vs 12.4 mo]) in patients (pts) with untreated EGFR-mutated mNSCLC. We report final overall survival (OS) outcomes for the intention-to-treat (ITT) population.

Sites randomized 449 eligible pts between Jan 2016 and Feb 2018 with an EGFR exon 19del or L858R mutation and no CNS metastases (1:1) to ERL (150 mg/day) with RAM (10 mg/kg q2w, n=224) or placebo (PBO, n=225). OS, a secondary endpoint, was to be analyzed at ~300 deaths. RELAY was not powered for OS.

Two hundred and ninety-seven deaths were reported at data cut-off (66% maturity). ERL+RAM showed numerically greater improvement in mOS vs ERL+PBO, at a median follow-up of 45.1 mo (IQR 26.70–71.20), in the ITT population (51.1 vs 46.0 mo: HR 0.98 [95% CI 0.78–1.24]). . ERL+RAM showed numeric improvement for OS in pts with a L858R vs Exon 19del mutation: ITT: L858R (n=204), mOS 51.6 vs 45.8 mo, HR 0.87 (95% CI 0.62–1.22). Exon 19del (n=243): mOS 49.0 vs 51.4 mo, HR 1.13 (95% CI 0.83–1.55).

The reported safety profile for ERL+RAM in this analysis was consistent with previous reports, with no increased toxicity noted over time.

Both ERL=RAM and ERL+PBO treatment arms reported long OS durations. The ERL+RAM arm demonstrated numerical improvement in mOS in the ITT population compared with the ERL+PBO arm. Data indicate that pts with L858R mutation derive more modest OS with EGFR-TKI monotherapy than the pts with Exon 19del, and might benefit from treatment intensification with ramucirumab.

DISCLOSURE

Originally presented at JSMO 2024

Publication History

Article published online:
18 March 2025