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. 


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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.

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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.