On May 29, 2020, the FDA approved the combination of Cyramza (ramucirumab; from Eli Lilly) in combination with Tarceva (erlotinib; from Astellas Pharma) for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) and an EGFR exon 19 deletions or exon 21 (L858R) mutations.
Cyramza and Tarceva were each previously approved by the FDA for the treatment of patients with metastatic NSCLC that has progressed after chemotherapy. This is the first time these therapies are approved as the first treatment of patients with NSCLC and EGFR mutations.
It is estimated that approximately 15% of patients diagnosed with NSCLC have an EGFR mutation.
The FDA approved the combination of Cyramza and Tarceva for first-line treatment of patients with NSCLC based on the phase 3 clinical trial RELAY, which included 449 patients with metastatic NSCLC whose tumors had EGFR exon 19 deletion or exon 21 (L858R) substitution mutations. None of the patients received treatment for NSCLC before.
“The approval of this new first-line metastatic EGFR-mutated non–small-cell lung cancer regimen, which inhibits the VEGFR and EGFR pathways together, is an important milestone in the treatment of this disease,” said Edward B. Garon, MD, David Geffen School of Medicine, University of California, and North America lead investigator of the RELAY clinical trial. “Ramucirumab [Cyramza], in combination with erlotinib [Tarceva], is a welcomed first-line option to offer our patients with metastatic EGFR-mutated non–small-cell lung cancer.”
The 449 patients in the study were randomized to receive Cyramza plus Tarceva or to placebo plus Tarceva. The average time without disease progression was 19.4 months with Cyramza and Tarceva compared with 12.4 months with placebo plus Tarceva. The overall response rate to therapy was 76% in the Cyramza and Tarceva group versus 75% in the placebo plus Tarceva group, with an average duration of response of 18 months with the combination versus 11.1 months in the placebo group.
At the time of the final analysis, the time without disease progression and overall survival data were not mature, meaning that many patients were still responding to therapy.
The most common side effects reported with Cyramza and Tarceva were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. The most common laboratory test abnormalities were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, neutropenia, increased alkaline phosphatase, and hypokalemia.
