Ramucirumab plus erlotinib in patients with untreated, EGFR‑mutated, advanced non‑small‑cell lung cancer (RELAY): a randomised, double‑blind, placebo‑controlled, phase 3 trial
Ramucirumab combined with erlotinib significantly improves progression‑free survival compared with erlotinib plus placebo in untreated EGFR‑mutated metastatic non‑small‑cell lung cancer patients (median PFS 19.7 months vs 12.7 months, HR 0.759, 95% CI 0.746‑0.776).
Background: Dual blockade of the EGFR and VEGF pathways in EGFR‑mutated metastatic non‑small‑cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR‑mutated metastatic NSCLC. Methods: This is a worldwide, double‑blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries. Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no CNS metastases. 449 eligible patients were randomly assigned 1:1 to receive oral erlotinib (150 mg/day) plus either intravenous ramucirumab (10 mg/kg) or matching placebo once every 2 weeks. The primary endpoint was investigator‑assessed progression‑free survival (PFS) in the intention‑to‑treat population. Findings: Progression‑free survival was significantly longer in the ramucirumab plus erlotinib group (median 19.7 months, 95% CI 15.4‑21.6) than in the placebo plus erlotinib group (12.7 months, 95% CI 11.0‑13.5), with a stratified hazard ratio of 0.759 (95% CI 0.746‑0.776; p<0.0001). Grade 3‑4 treatment‑emergent adverse events occurred in 72% of patients in the ramucirumab group versus 54% in the placebo group, most commonly hypertension and acneiform dermatitis. Interpretation: Ramucirumab plus erlotinib demonstrated superior PFS compared with placebo plus erlotinib in patients with untreated EGFR‑mutated metastatic NSCLC and has a safety profile consistent with that of the individual agents. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR‑mutated metastatic NSCLC.
The study establishes a new first‑line combination therapy that significantly extends progression‑free survival in EGFR‑mutated metastatic NSCLC, providing a clinically meaningful treatment advance and confirming the benefit of dual EGFR and VEGF pathway inhibition.
Evidence level: Irányelv / elfogadott gyakorlat. Magas szintű klinikai elfogadottság.
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