Mutation Confers Anti-EGFR Resistance

Published: Friday, Sep 14, 2012

EGFR proteinA common mutation in non-small cell lung cancer confers resistance to tyrosine kinase inhibitors and worsens survival, creating a need for an alternative approach to treating the subgroup of patients with the mutation, a review of almost 1100 patient records showed.

Patients with exon 20 insertion mutations in epidermal growth factor receptor (EGFR) had a 60% shorter time to treatment failure with an EGFR inhibitor than after initial platinum-based chemotherapy. They also had a 50% lower overall survival rate as compared with patients who had other common EGFR mutations.

Patients with exon 20 insertions had a median survival similar to that of patients with wild-type EGFR, Peter Lo, said at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology.

“Although patients with EGFR exon 20 insertions have characteristics similar to those of patients with other types of EGFR mutations, we found that exon 20 insertions were associated with a worse survival,” said Lo, a research data specialist at Dana-Farber Cancer Institute in Boston, Massachusetts. “The lack of structural consistency between different insertion variants indicates a varied biology among this family of mutations.”

Exon 20 insertions are the third most common group of EGFR mutations in NSCLC. Cancers harboring exon 20 insertions are thought to be insensitive to the tyrosine kinase inhibitors erlotinib and gefitinib. Otherwise, little is known about clinical behavior of the mutations, said Lo.

In an effort to determine more about the behavior of exon 20 insertions, investigators reviewed medical records of 1,086 patients whose NSCLC had undergone EGFR sequencing. The sequencing results showed that 27 patients had tumors harboring exon 20 insertions, representing 13 distinct variants. Exon 20 insertions accounted for 9% of all EGFR mutations identified in the cohort.

Treatment data available for 19 patients with exon 20 insertions showed they received 34 different treatments for advanced NSCLC. Median time to treatment failure was 5.9 months with platinum-based combination chemotherapy but was shorter with erlotinib (2.4 months) and other chemotherapy (2.3 months).

Survival analysis for 839 patients showed that patients with exon 20 insertions had a median overall survival of 16.5 months compared with 33 months for patients with other EGFR mutations.

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