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Predictors of the response to gefitinib in refractory non-small cell lung cancer
Kyu-Sik Kim1, Ju-Yeon Jeong, Young-Chul Kim
1Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun, Jeollanam-do, 519-809 South Korea.
Abstract:
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has a response rate of 10% to 20% in refractory non-small cell lung carcinoma. Although female gender, adenocarcinoma, and never having smoked are possible markers of a favorable response, mutations of the EGFR gene have also been reported to be highly significant predictors of response. Seventy patients with relapsed non-small cell lung carcinoma were enrolled in the Expanded Access Program. After the drug became available commercially, 28 more patients were treated with gefitinib. Response evaluations were feasible in 80 patients. Twenty-seven tumor specimens (8 responders and 19 nonresponders) were available for the sequence analysis of the EGFR gene. The response rate was 25% (20/80) and the disease control rate (remission + stable disease) was 47.5% (38/80). The response rate was significantly higher for adenocarcinoma (41.0%) versus non-adenocarcinoma (9.8%, P = 0.001), in those who never smoked (58.8%) versus smokers (15.9%, P < 0.001), and in females (42.1%) versus males (19.7%, P = 0.049). A deletion or mutation of the EGFR gene was found in six of eight responders. Remission was noted in all patients with a mutation, whereas the response rate was 9.5% (2/21) in patients without a mutation (P < 0.001). The predictors of response showed significant correlations with survival and time to progression. In a multivariate logistic analysis, the independent predictors of response were smoking history and adenocarcinoma. Given that 9.5% of smokers and 6.7% of those with non-adenocarcinoma showed a mutation of the EGFR gene, the genetic profile may replace those variables as an independent predictor of a response.
Insights
Gefitinib shows promise in non-small cell lung cancer, with EGFR mutations significantly predicting response. Genetic profiling may become a key factor in treatment selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gefitinib, an EGFR tyrosine kinase inhibitor, has limited efficacy in refractory non-small cell lung carcinoma (NSCLC).
- Previous studies suggest female gender, adenocarcinoma histology, and never-smoking status are potential response predictors.
- EGFR gene mutations are increasingly recognized as significant predictors of gefitinib response.
Purpose of the Study:
- To evaluate the response rate of gefitinib in patients with relapsed non-small cell lung carcinoma.
- To identify clinical and genetic predictors of gefitinib response.
- To assess the correlation between EGFR gene mutations and treatment outcomes.
Main Methods:
- Eighty patients with relapsed NSCLC were treated with gefitinib.
- Tumor specimens from 27 patients underwent EGFR gene sequence analysis.
- Response evaluations included remission and stable disease.
- Multivariate logistic analysis was used to identify independent predictors of response.
Main Results:
- The overall response rate to gefitinib was 25% (20/80), with a disease control rate of 47.5%.
- Higher response rates were observed in patients with adenocarcinoma (41.0%), never-smokers (58.8%), and females (42.1%).
- EGFR gene mutations were detected in six of eight responders, and all patients with a mutation achieved remission. The response rate was significantly higher in patients with EGFR mutations (P < 0.001).
Conclusions:
- Gefitinib demonstrates a notable response rate in relapsed NSCLC, particularly in specific patient subgroups.
- EGFR gene mutations are a strong predictor of gefitinib response and remission.
- Genetic profiling, specifically EGFR mutation status, may serve as an independent predictor of response, potentially surpassing traditional clinical variables.
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