Adding Erlotinib to Chemoradiation Improves Overall Survival but not Progression-Free Survival in Stage III Non-Small-Cell Lung Cancer

BACKGROUND: Concurrent chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC) for patients who can tolerate it. We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy without increasing toxicity in a single-arm prospective phase II trial. METHODS: Forty-eight patients with previously untreated NSCLC received intensity-modulated radiation therapy (63 Gy/35 fractions) on Monday–Friday, with chemotherapy (paclitaxel 45 mg/m(2), carboplatin AUC=2) on Mondays, for 7 weeks. All patients also received the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (150 mg orally 1/day) on Tuesday–Sunday for 7 weeks followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. RESULTS: Of 46 patients evaluable for response, 40 were former or never-smokers and 41 were evaluable for EGFR mutations (37 wild-type [wt] and 4 [mutated; all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, one grade 4, eleven grade 3). Twelve patients (26%) had complete responses (10 wt, 2 mutated), 27 (59%) partial (21 wt, 2 mutated, 4 unknown), and 7 (15%) none (6 wt, 2 mutated, 1 unknown) (P=0.610). At 37.0 months’ follow-up (range 3.6–76.5 months) for all patients, median OS time was 36.5 months and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%; none differed by mutation status. Twelve patients had no progression and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 wt, 3 mutated, 1 unknown). CONCLUSIONS: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.