The FDA has approved ramucirumab (Cyramza®, Eli Lilly and Company) in combination with erlotinib for patients with previously untreated advanced non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 substitution mutation.
The approval was based on RELAY (NCT02411448), a phase 3 trial that enrolled 449 patients with untreated stage IV NSCLC. Eligible patients were at least 18 years old, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had an EGFR exon 19 deletion or exon 21 substitution mutation. Patients were randomized in a 1:1 ratio to receive ramucirumab 10 mg/kg or placebo administered intravenously once every two weeks, in combination with erlotinib 150 mg taken orally once daily until progression or unacceptable toxicity. The study's primary end point was progression-free survival, with secondary end points of overall survival, overall response rate, and duration of response.
At a median follow-up of 20.7 months, ramucirumab/erlotinib significantly increased median progression-free survival compared with placebo/erlotinib (19.4 vs 12.4 months). Ramucirumab/erlotinib also produced a higher overall response rate (76% vs 75%) and median duration of response (18.0 months vs 11.1 months) compared with the control group. Median overall survival was not yet reached at the time of the final analysis.
The most frequent treatment-related adverse events occurring in at least 20% of patients receiving ramucirumab/erlotinib included infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. The most frequent laboratory abnormalities experienced by at least 20% of patients treated with ramucirumab/erlotinib included increased aspartate aminotransferase/alanine aminotransferase (AST/ALT), anemia, thrombocytopenia, neutropenia, increased alkaline phosphatase, and hypokalemia.
"Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC," concluded RELAY's investigators, led by Kazuhiko Nakagawa, MD, Professor of Medical Oncology at Kindai University in Osaka, Japan, in their publication in The Lancet Oncology this past December. "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."
The recommended dose of ramucirumab is 10 mg/kg intravenously every two weeks in combination with 150 mg taken orally once daily.
For More Information
Nakagawa K, Garon EB, Seto T, et al (2019). 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. Lancet Oncol, 20(12)1655-1669. DOI:10.1016/S1470-2045(19)30634-5
Clinicaltrials.gov (2020). A study of ramucirumab (LY3009806) in combination with erlotinib in previously untreated participants with EGFR mutation-positive metastatic NSCLC (RELAY) (RELAY). NLM identifier: NCT02411448.
US Food & Drug Administration (2020). FDA approves ramucirumab plus erlotinib for first-line metastatic NSCLC. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-ramucirumab-plus-erlotinib-first-line-metastatic-nsclc
Image credit: Scott Wilkinson and Adam Marcus. Courtesy of the National Cancer Institute