On May 29, the U.S. Food and Drug Administration (FDA) approved ramucirumab (Cyramza, injection, 10 mg/mL solution) in combination with erlotinib for the first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.
Ramucirumab plus erlotinib is the first and only FDA-approved anti–vascular endothelial growth factor (VEGF) receptor/EGFR tyrosine kinase inhibitor combination therapy for metastatic EGFR-mutated NSCLC.
RELAY Trial
This approval is based on efficacy and safety data from the global, randomized, placebo-controlled phase III RELAY trial. Initiated in 2015, the study randomly assigned 449 patients across North America, Europe, and Asia. The primary endpoint of the RELAY trial is progression-free survival; key secondary endpoints include safety, overall response rate, duration of response, and overall survival.
In the RELAY study, treatment with ramucirumab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared to placebo in combination with erlotinib (19.4 months in the ramucirumab-containing arm compared to 12.4 months in the placebo-containing arm [hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.46–0.76, P < .0001]). The progression-free survival treatment effect was consistent across exon 19 and exon 21 subgroups.
At the time of the final analysis of progression-free survival, overall survival data were not mature, as only 26% of planned events for the final analysis had occurred (HR = 0.83, 95% CI = 0.53–1.30). A final overall survival analysis is planned when at least 300 events have occurred.
The overall safety profile observed in the RELAY study was consistent with that of its individual components. The most common adverse reactions (all grades) observed in patients treated with ramucirumab plus erlotinib at a rate of ≥ 30% of patients and ≥ 2% higher than patients treated with placebo plus erlotinib were infections, hypertension, stomatitis, proteinuria, alopecia, and epistaxis. The most common laboratory abnormalities ≥ 30% and ≥ 2% higher than the placebo were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, and neutropenia.
