As reported in The Lancet Oncology by Nakagawa et al, the phase III RELAY trial has shown that the addition of the VEGFR2 inhibitor ramucirumab to the EGFR inhibitor erlotinib improved progression-free survival in treatment-naive, advanced EGFR-mutated non–small cell lung cancer (NSCLC).

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Study Details

In the double-blind trial, 449 patients from 100 sites in 13 countries were randomly assigned between January 2016 and February 2018 to receive ramucirumab/erlotinib (n = 224) or placebo/erlotinib (n = 225). Eligible patients had an EGFR exon 19 deletion or exon 21 substitution mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no central nervous system metastases.

Treatment consisted of erlotinib 150 mg/d, plus either intravenous ramucirumab 10 mg/kg or matching placebo once every 2 weeks. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Disease was stage IV in 87% of the ramucirumab/erlotinib group and 84% of the placebo/erlotinib group, and 77% of patients in each group were Asian.

Progression-Free Survival

Median follow-up was 20.7 months. Median progression-free survival was 19.4 months in the ramucirumab/erlotinib group vs 12.4 months in the placebo/erlotinib group (stratified hazard ratio [HR] = 0.59, P < .0001). Progression-free survival at 1 year was 71.9% vs 50.7%. Analysis according to independent radiologic review in 440 patients showed a median progression-free survival of 16.5 months vs 11.1 months (HR = 0.671, 95% confidence interval = 0.518–0.869).

Overall survival data were not mature at interim analysis. Overall survival was 93% vs 94% at 1 year and 83% vs 79% at 2 years. Overall response rates were 76% (complete response in 1%) vs 75% (complete response in 1%), with median durations of response of 18.0 vs 11.1 months.  

Adverse Events

Grade 3 or 4 adverse events were reported in 72% of patients in the ramucirumab/erlotinib group vs 54% of the placebo/erlotinib group. The most common adverse events in the ramucirumab/erlotinib group were hypertension (24%, all grade 3) and dermatitis acneiform (15%); the most common in the placebo/erlotinib group were dermatitis acneiform (9%) and increased alanine aminotransferase (8%). Serious adverse events were reported in 29% vs 21% of patients; the most common in the ramucirumab/erlotinib group were pneumonia (3%), cellulitis (2%), and pneumothorax (2%); the most common in the placebo/erlotinib group were pyrexia (2%) and pneumothorax (1%). One patient in the ramucirumab/erlotinib group died from an adverse event considered related to study treatment (hemothorax after thoracic drainage procedure for pleural empyema).

The investigators concluded, “Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC. Safety was consistent with the safety profiles of the individual compounds in advanced lung cancer. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC.”

Kazuhiko Nakagawa, MD, of the Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Eli Lilly. For full disclosures of the study authors, visit thelancet.com.