FDA Approves Cyramza plus Tarceva for First-Line Treatment of Metastatic NSCLC with EGFR Mutation

Web Exclusives - FDA Updates, Lung Cancer

On May 29, 2020, the FDA approved ramucirumab (Cyramza; Eli Lilly) in combination with erlotinib (Tarceva) for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR ) exon 19 deletions or exon 21 (L858R) mutations. Ramucirumab was previously approved by the FDA as monotherapy and in combination with other therapies for several types of cancer, including metastatic NSCLC, in combination with docetaxel, for patients whose disease progressed after treatment with platinum-based chemotherapy.

“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. It is wonderful that patients now have multiple options for initial therapy capable of delaying disease progression for considerably longer than erlotinib, which has been our traditional standard approach,” said Edward Garon, MD, David Geffen School of Medicine, University of California, and North America lead investigator of the RELAY clinical trial. “Ramucirumab, in combination with erlotinib, is a welcomed first-line option to offer our patients with metastatic EGFR-mutated non–small-cell lung cancer.”

It is estimated that approximately 15% of patients diagnosed with NSCLC have an EGFR mutation.

The efficacy of ramucirumab plus erlotinib for first-line treatment of patients with NSCLC was based on the results of the phase 3 clinical trial RELAY, a multinational, randomized, double-blind, placebo-controlled, multicenter study in treatment-naïve patients with metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations.

The study included 449 patients who were randomized in a 1:1 ratio to intravenous ramucirumab 10 mg/kg, in combination with erlotinib 150 mg orally once daily, or to placebo every 2 weeks plus erlotinib 150 mg orally once daily, until disease progression or unacceptable toxicity. The major efficacy end point was progression-free survival (PFS) as assessed by the investigator (RECIST 1.1). Additional efficacy outcome measures included overall survival (OS), overall response rate (ORR), and duration of response (DOR).

The median PFS was 19.4 months in the ramucirumab plus erlotinib arm compared with 12.4 months in the placebo plus erlotinib arm (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.46-0.76; P <.0001). The ORR was 76% in the ramucirumab plus erlotinib arm versus 75% in the placebo plus erlotinib arm, with median DOR of 18 months and 11.1 months, respectively. At the time of the final analysis, the PFS and OS data were not mature; with only 26% of the deaths required for the final analysis occurring by that time (HR, 0.83; 95% CI, 0.53-1.30).

The most common (≥20%) adverse events reported with ramucirumab plus erlotinib at a rate of ≥2% versus the placebo arm were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. The most common (≥20%) laboratory abnormalities at a rate of ≥2% higher than in the placebo arm were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, neutropenia, increased alkaline phosphatase, and hypokalemia.

The recommended dose of ramucirumab for metastatic NSCLC in combination with erlotinib is 10 mg/kg every 2 weeks.

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Last modified: June 8, 2020