Richard Pazdur, MD
The FDA has approved the VEGFR-2 inhibitor ramucirumab (Cyramza) in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumor has progressed during or following treatment with platinum-based chemotherapy.
The approval was based on findings of the phase III REVEL trial, which showed a 1.4-month improvement in overall survival (OS) when comparing the combination with docetaxel alone. Median OS was 10.5 months in the combination arm compared with 9.1 months in the docetaxel-alone arm (hazard ratio [HR] = 0.857; 95% CI, 0.751-0.98; P
“Today’s approval is the third indication that Cyramza has received in 2014,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in a statement. "The commitment to study Cyramza in a variety of malignancies provides important treatment options to patients.”
Progression-free survival (PFS) was also improved with the combination: Median PFS was 4.5 months with the combination and 3.0 months with docetaxel alone (HR = 0.762; 95% CI, 0.68-0.86; P
The trial enrolled 1253 patients with squamous (26.2%) and nonsquamous (73.8%) stage 4 disease (ECOG performance status ≤1). Patients were randomized 1:1 to 75 mg/m2 of docetaxel in combination with 10 mg/kg of ramucirumab (n = 628) or placebo (n = 625) on day 1 of a 3-week cycle. Patients were treated until disease progression or unacceptable toxicity.
Safety was evaluated in 1245 patients who received at least one dose of ramucirumab. In general, there was a “minimal and manageable increased risk” with the combination, lead study author Maurice Pérol, MD, head of Thoracic Oncology at Cancer Research Center of Lyon in France, said at a press briefing during the 2014 ASCO Annual Meeting.
The most commonly reported grade ≥3 adverse events in the combination arm were neutropenia (34.9%), febrile neutropenia (15.9%), fatigue (11.3%), leukopenia (8.5%), hypertension (5.4%), and pneumonia (5.1%). The rate of adverse event-associated deaths in the combination arm (5.4%) was comparable to the docetaxel alone arm (5.8%).
Ramucirumab, which is marketed by Eli Lilly and Company, was recently approved by the FDA in November 2014 for use in combination with paclitaxel to treat patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Ramucirumab was approved in April 2014 for use as a single agent to treat patients with advanced gastric or GEJ adenocarcinoma that did not respond to, or had progressed following, first-line therapy with platinum- or fluoropyrimidine-containing chemotherapy. The agent has also been looked at in HER2-negative metastatic breast cancer, but it failed to delay disease progression in a phase III trial.