RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC

Introduction: RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46–0.76, p < 0.0001; median progression-free survival: 19.4 versus 12.4 mo). Here, we report the final overall survival (OS; secondary end point) outcomes for the intention-to-treat population. Methods: Between January 2016 and February 2018, 449 eligible patients with an EGFR exon 19del or L858R mutation and no central nervous system metastases were randomized (1:1) to ERL (150 mg/day) with RAM (10 mg/kg every two weeks, N = 224) or placebo (N = 225). Results: At data cutoff, 297 deaths were reported (overall event rate = 66%), with a median follow-up of 45.1 months (interquartile range: 26.7–71.2), an OS HR of 0.98 (95% CI: 0.78–1.24, p = 0.864), and median OS of 51.1 months (RAM + ERL) and 46.0 months (placebo + ERL). Outcomes in subsets of patients with poor prognosis (L858R or TP53 co-mutation) suggest a directional improvement in OS (L858R: HR = 0.87, 95% CI: 0.62–1.22; exon 19del: HR = 1.13, 95% CI: 0.83–1.55; TP53 co-mutation: HR = 0.83, 95% CI: 0.58–1.19; TP53-wild-type: HR = 1.22, 95% CI: 0.87–1.72). Treatment-emergent T790M rates were similar between arms. Over 80% of patients received post-study discontinuation therapy (>50% received osimertinib in comparable numbers between arms). The safety profile for RAM + ERL was consistent with previous reports with no increased toxicity over time or new safety signals observed. Conclusion: In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms. Clinical Trial Information: ClinicalTrials.gov