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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000141
Original Articles

Relationship Between EGFR Expression, EGFR Mutation Status, and the Efficacy of Chemotherapy Plus Cetuximab in FLEX Study Patients with Advanced Non–Small-Cell Lung Cancer

Douillard, Jean-Yves MD, PhD*; Pirker, Robert MD; O’Byrne, Kenneth J. MD; Kerr, Keith M. FRCPath§; Störkel, Stephan MD; von Heydebreck, Anja PhD; Grote, Hans Jürgen MD#; Celik, Ilhan MD**; Shepherd, Frances A. MD††

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Abstract

Introduction:

The phase III FLEX study (NCT00148798) in advanced non–small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of ≥200; scale 0–300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status.

Methods:

A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status.

Results:

Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of ≥200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status.

Conclusions:

The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non–small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Copyright © 2014 by the International Association for the Study of Lung Cancer

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