Combination Cyramza and Tarceva Approved for First-Line Treatment of Metastatic NSCLC with EGFR Mutation

Ramucirumab had been approved previously as monotherapy and in combination with other therapies for metastatic non–small-cell lung cancer (NSCLC) and several other cancers, in combination with docetaxel, for patients with disease progression after receiving 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.”

The efficacy of ramucirumab plus erlotinib for first-line treatment of patients with NSCLC was demonstrated in the results of the phase 3 clinical trial RELAY, a multinational, randomized, double-blind, placebo-controlled study in treatment-naïve patients with metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations. It is estimated that approximately 15% of patients diagnosed with NSCLC have an EGFR mutation.

For the study, 449 patients were randomized in a 1:1 ratio to combination treatment with intravenous ramucirumab 10 mg/kg plus once-daily oral erlotinib 150 mg, or to placebo every 2 weeks plus once-daily oral erlotinib 150 mg, until disease progression or unacceptable toxicity. Investigator-assessed (RECIST 1.1) progression-free survival (PFS) was the study’s major efficacy end point. Overall survival (OS), overall response rate (ORR), and duration of response (DOR) were among additional efficacy outcome measures assessed by the investigators.

The ramucirumab plus erlotinib arm had a median PFS of 19.4 months, 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). ORR was comparable in both arms (76% in the ramucirumab plus erlotinib arm vs 75% in the placebo plus erlotinib arm). The ramucirumab plus erlotinib group had a median DOR of 18 months, compared with 11.1 months for the placebo plus erlotinib group. At the time of 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. Increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, neutropenia, increased alkaline phosphatase, and hypokalemia were the most common (≥20%) laboratory abnormalities at a rate of ≥2% higher than in the placebo arm.