EGFR MutationImpact on DefinitiveConcurrent Chemoradiation Therapy for Inoperable Stage III Adenocarcinoma.

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.