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

Science and Research

BACKGROUND: RELAY, a global double-blind, placebo-controlled Phase 3 study (NCT02411448) demonstrated statistically significant improvement in progression-free survival (PFS; primary endpoint) for ramucirumab (RAM)+erlotinib (ERL) in patients with untreated EGFR-mutated metastatic NSCLC: HR 0.59 (95%CI: 0.46-0.76, p<0.0001; median [m]PFS 19.4 versus 12.4 months). Here, we report final overall survival (OS; secondary endpoint) outcomes for the intention-to-treat (ITT) population. METHODS: Between Jan.2016 and Feb.2018, 449 eligible patients with an EGFR exon 19del or L858R mutation and no CNS metastases were randomized (1:1) to ERL (150 mg/day) with RAM (10 mg/kg q2w, n=224) or placebo (PBO, n=225). RESULTS: At data cut-off, 297 deaths were reported (overall event-rate 66%), median follow-up; 45.1 months (IQR: 26.7-71.2), OS HR; 0.98 (95%CI: 0.78-1.24, p=0.864), mOS; 51.1 (RAM+ERL) and 46.0 (PBO+ERL) months. Outcomes in subsets of poor prognostic patients (L858R or TP53 co-mutation) suggest a directional improvement in OS (L858R; HR [95%CI] 0.87 [0.62-1.22], exon 19del; 1.13 [0.83-1.55], TP53 co-mutation; 0.83 [0.58-1.19], TP53-wild-type; 1.22 [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). 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.