Reconsideration of Gefitinib in EGFR-Mutant NSCLC

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In May 2003, the EGFR TKI gefitinib received an accelerated approval from the FDA as a treatment for patients with non-small cell lung cancer (NSCLC), based on an improvement an overall response rate of approximately 10%. However, following negative findings from two clinical trials, the approval was scaled back to include only patients who benefited from previous treatment with gefitinib and new patients in clinical trials.

At the time of the initial approval of gefitinib, the role of the EGFR mutation in NSCLC was not yet fully understood, notes Mark Socinski, MD. However, since this time, clinical trials have shown that gefitinib is an effective agent for patients with EGFR-mutated NSCLC. The efficacy seen with this agent is similar to the EGFR TKIs erlotinib and afatinib, Socinski suggests.

The recommended dose for gefitinib of 250 mg was established based on biologic responses and not toxicity. As a result, the commonly used 250 mg dose of gefitinib is only about one-third of the maximum tolerated dose, resulting in fewer side effects. This lower toxicity and similar effectiveness could give gefitinib an advantage, Socinski believes.

If a full approval were given to gefitinib in the United States for the frontline treatment of patients with EGFR-positive NSCLC it would create competition in the market and potentially lower costs, Socinski believes. Treatment selection for patients with EGFR-mutations would likely be based on cost and toxicity concerns, as opposed to efficacy.