FDA Approves Gefitinib for EGFR-Mutated Metastatic Non–Small Cell Lung Cancer
The U.S. Food and Drug Administration (FDA) has approved gefitinib (Iressa) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. This approval of gefitinib is being approved concurrently with a labeling expansion of the therascreen EGFR RGQ PCR Kit, a companion diagnostic test for patient selection.
Study Results
The approval of gefitinib was based on the results of a multicenter, single-arm, open-label clinical study of a total of 106 treatment-naive patients with metastatic EGFR mutation–positive NSCLC who received gefitinib at a dose of 250 mg daily until disease progression or intolerable toxicity. The major efficacy outcome was objective response rate according to RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 as evaluated by both a blinded independent central review and investigators.
The blinded independent central review objective response rate was 50% (95% confidence interval [CI] = 41%–59%), with a median duration of response of 6.0 months. Investigator-determined objective response rate was 70% (95% CI = 61%–78%), with a median duration of response of 8.3 months.
Efficacy results were supported by an exploratory analysis of a subset of a randomized, multicenter, open-label trial conducted in patients with metastatic adenocarcinoma histology NSCLC receiving first-line treatment. Patients were randomly assigned (1:1) to receive gefitinib 250 mg once daily or up to six cycles of carboplatin/paclitaxel. The efficacy outcomes included progression-free survival and objective response rate as assessed by the blinded independent central review.
The subset population consisted of 186 of 1,217 patients (15%) determined to be EGFR-positive and had radiographic scans available for a retrospective assessment by a blinded independent central review. In this subset, there were 88 gefitinib-treated patients and 98 carboplatin/paclitaxel-treated patients.
The hazard ratio for progression-free survival in the gefitinib-treated arm was 0.54 (95% CI = 0.38–0.79), with a median progression-free survival of 10.9 months for the gefitinib-treated patients and 7.4 months for the carboplatin/paclitaxel-treated patients as assessed by blinded independent central review. In addition, the blinded independent central review objective response rate was 67% (95% CI = 56%–77%), with responses lasting 9.6 months for gefitinib-treated patients, and 41% (95% CI = 31%–51%), with responses lasting 5.5 months for carboplatin/paclitaxel-treated patients.
Safety Data
Safety data were evaluated for common adverse reactions in a double-blind placebo- controlled trial of 1,692 patients. Of the 1,129 patients who received gefitinib, the most common (≥ 20%) adverse reactions in order of decreasing frequency were skin reactions, increase in aspartate aminotransferase (AST), increase in alanine aminotransferase (ALT), proteinuria, and diarrhea. The most common (≥ 2%) grade 3 to 4 adverse reactions were proteinuria, diarrhea, increased ALT, decreased appetite, increased AST, and skin reactions. Approximately 5% of gefitinib-treated patients discontinued treatment due to an adverse reaction.
Serious and uncommon adverse drug reactions were evaluated in 2,462 patients with NSCLC who received gefitinib monotherapy in three randomized clinical studies. They included interstitial lung disease (1.3% ), fatal hepatotoxicity (0.04%), and grade 3 ocular disorders (0.1%).
The recommended dose of gefitinib is 250 mg orally once daily with or without food. Treatment should continue until disease progression or unacceptable toxicity.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
