EGFR MutationImpact on DefinitiveConcurrent Chemoradiation Therapy for Inoperable Stage III Adenocarcinoma

Kosuke Tanaka, Toyoaki Hida, Yuko Oya, Tomoyo Oguri, Tatsuya Yoshida, Junichi Shimizu, Yoshitsugu Horio, Akito Hata, Reiko Kaji, 2Shiro Fujita, Yoshitaka Sekido, Takeshi Kodaira, Masaki Kokubo, Nobuyuki Katakami, Yasushi Yatabe
Journal of Thoracic Oncology 2015 September 2

BACKGROUND: Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma; however, little has been reported about the impact of EGFR mutation on CRT efficacy.

METHODS: From 2006-2013, we retrospectively screened 104 unresectable stage III adenocarcinoma patients who were examined for EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet chemotherapy in first-line setting, and compared the clinical outcomes and recurrence patterns according to mutation status.

RESULTS: Among 104 patients, EGFR mutation was detected in 29 (28%). The overall response rate did not differ between EGFR-mutant and wild-type patients (72.4% vs. 72.0%, p=0.607). The median progression-free survival (PFS) in concurrent CRT was significantly shorter in EGFR-mutant patients than in wild-type patients (9.8 [95%CI: 7.6-19.0] vs. 16.5 [95%CI: 11.8-19.9] months, p=0.041). The 2-year recurrence-free survival rate was 7.7% and 28.1% in EGFR-mutant and wild-type patients, respectively (p=0.028). Distant metastases were more frequently identified as the first recurrence site in EGFR-mutant patients than in wild-type patients (76% vs. 40%, p=0.001). The brain was the most commonly affected site in EGFR-mutant patients (35%). However, locoregional recurrence was less common in EGFR-mutant patients than in the wild-type population (14% vs. 35%, p=0.027). Overall survival (OS) was similar between EGFR-mutant and wild-type patients (51.1 [95%CI: 28.2-70.2] vs. 42.9 [95%CI: 35.3-NA] months, p=0.637). Among the EGFR wild-type population who were examined for Kras mutation, Kras-mutant patients had significantly worse OS than Kras wild-type patients (21.6 vs. 49.8 months, p=0.024).

CONCLUSION: Concurrent CRT resulted in shorter PFS in EGFR-mutant stage III adenocarcinoma patients than in wild-type patients, mainly due to distant metastasis relapse, regardless of better local control. Because of these distinct biological features, a different strategy, including EGFR-TKIs for EGFR-mutant, locally advanced adenocarcinoma patients receiving definitive CRT may be needed.

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