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

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.

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).

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.

In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.

ClinicalTrials.gov Identifier: NCT02411448.