EGFR Mutation Abundance Affects Therapy in NSCLC

Progression-free survival significantly longer in patients with high abundance of EGFR mutations

THURSDAY, July 28 (HealthDay News) -- The abundance of epidermal growth factor receptor (EGFR) mutations in advanced non-small-cell lung cancer (NSCLC) is associated with a response to treatment with the EGFR-tyrosine kinase inhibitor (TKI), gefitinib, according to a study published online July 25 in the Journal of Clinical Oncology.

Qing Zhou, from the Guangdong General Hospital and Guangdong Academy of Medical Sciences in Guangzhou, China, and colleagues determined whether the abundance of EGFR mutations predicts clinical benefit from gefitinib. Using direct DNA sequencing and the amplification refractory mutation system (ARMS), EGFR mutations were detected in 100 lung cancer samples. Tumors with low mutation abundance were positive by ARMS but negative by direct DNA sequencing, and tumors with high mutation abundance were positive by both methods. Tumors carrying wild-type EGFR were negative by both methods. All patients were treated with gefitinib, and the correlation between mutation abundance and response to therapy was assessed.

The investigators found that 51, 18, and 31 samples harbored high abundances of EGFR mutations, low abundances of EGFR mutations, and wild-type EGFR, respectively. The median progression-free survival was significantly longer in the high abundance EGFR-mutation group, compared to the low abundance group, and significantly longer in the low abundance group, compared to patients with wild-type tumors (11.3, 6.9, 2.1 months, respectively). The objective response rates (ORRs) were 62.7, 44.4, and 16.1 percent for high abundance mutations, low abundance mutations, and wild type, respectively. The overall survival (OS) rates for the three groups were 15.9, 10.9, and 8.7 months, respectively. The difference between patients with high and low EGFR mutation abundance was not significant regarding ORR and OS.

"The relative abundance of EGFR mutations could predict the extent of benefit from EGFR-TKI treatment for advanced NSCLC," the authors write.

One of the study authors disclosed financial ties to AstraZeneca.

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