The Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted 6 to 5 that ramucirumab (Cyramza; Lilly) plus erlotinib demonstrated a favorable benefit/risk profile for patients with untreated metastatic epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC).
The vote was based on data from the phase 3 RELAY study (N=449), which evaluated the efficacy and safety of ramucirumab in combination with erlotinib in previously untreated patients with metastatic EGFR-mutated NSCLC. Findings from the study showed that treatment with the combination resulted in a statistically significant improvement in median PFS (primary end point) compared with placebo plus erlotinib (19.4 months vs 12.4 months, respectively; HR 0.59; 95% CI, 0.46-0.79; P ≤.0001).
However, in meeting documents, further follow-up of overall survival data (which had been immature at the time of analysis) showed a hazard ratio of 0.92 (95% CI, 0.65-1.32). “Given the upper limit of the confidence interval of 1.3, the results suggest a possible detrimental effect on survival for patients treated with the combination of ramucirumab and erlotinib,” the panel noted. Adding that “In the context of an add-on therapy associated with increased toxicity, FDA considers this a safety concern.”
With regard to safety, data from the trial showed increased toxicity with the combination compared with erlotinib alone, with a higher incidence of grade ≥3 adverse events (72% vs 54%) and serious adverse events (29% vs 21%) reported. Adverse events occurring at a higher incidence in the ramucirumab plus erlotinib arm included bleeding/hemorrhage, hypertension, proteinuria, and severe infections.
The panel concluded that “While the first-line treatment of patients with EGFR-positive NSCLC remains an unmet medical need, there are therapies currently approved for which an improvement in [overall survival] has been observed when compared to first generation EGFR [tyrosine kinase inhibitors].”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval.
Commenting on the meeting outcome, Maura Dickler, MD, vice president of late phase development, Lilly Oncology, said: “Given the unmet need that remains in treating metastatic EGFR-mutated non-small cell lung cancer, we are encouraged that the majority of these experts agree Cyramza plus erlotinib has a favorable benefit/risk profile for the first-line treatment of these patients.”
Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist that is currently indicated to treat gastric cancer, colorectal cancer, non-small cell lung cancer (in combination with docetaxel), and hepatocellular carcinoma.
For more information visit fda.gov.