Chemotherapy Decreases Rate of EGFR Mutation in NSCLC

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(ChemotherapyAdvisor) – Use of chemotherapy in patients with non-small cell lung cancer (NSCLC) may affect EGFR mutation status by reducing mutation frequency, according to a study in the Journal of Clinical Oncology online July 23.

Since EGFR mutation can predict response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with NSCLC, Jie Wang, MD, PhD, of the Beijing Cancer Hospital and Institute, Beijing, China, and colleagues sought to determine the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC.

Three cohorts provided samples: the first cohort comprised 264 patients with advanced NSCLC who had received first-line chemotherapy for whom matched blood samples pre- and postchemotherapy were available; the second cohort comprised 63 patients with stage IIB to IIIB disease who had pre- and postneoadjuvant chemotherapy tumor tissue samples; and the third cohort, 79 patients with advanced NSCLC treated with palliative surgery. The potential effect of chemotherapy was assessed following determination of EGFR mutation status.

Results from the first cohort showed EGFR mutations in 91 (34.5%) of the prechemotherapy plasma and 61 (23.1%) of the postchemotherapy plasma samples; this decrease in EGFR mutation rate was statistically significant (P<0.001). “Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response than patients with a reverse change (P=0.037),” the investigators wrote.

Similarly, in the second cohort, EGFR mutation rate decreased in 22 tissues (34.9%) after neoadjuvant chemotherapy compared with presence of EGFR mutations in 12 prior to treatment (19.0%; P=0.013). In the third cohort, 38.0% of patients showed an intratumor heterogeneity of EGFR mutation vs 62.0% that were homogeneous, either with an EGFR mutation or no mutation.

“This observation may be attributable to the heterogeneity of intratumoral EGFR mutations and the different sensitivities of EGFR-mutated and wild-type tumor cells to chemotherapy,” the investigators concluded. “These findings should be considered in future studies designed to elucidate the predictive role of EGFR mutation in second-line TKI therapy for patients with NSCLC.”


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