Final Results of a Prospective Phase 2 Study of Adding Erlotinib to Chemoradiation for patients With Stage III Non–small Cell Lung Cancer

Abstract

Concurrent chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC) patients. We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy, since we have demonstrated radiation sensitization by erlotinib in preclinical setting using mice model. 48 patients with stage III NSCLC, PS 0-1, received radiotherapy (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m2, carboplatin AUC=2) on Mondays, for 7 weeks. All patients also received EGFR-TKI 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. 46 out of 48 patients were evaluable for response, 40 were former or never smoker and 41 were evaluated for EGFR mutation status: 37 wild-type and 4 were found to have mutation ( 3 exon 19 deletion, 1 exon 21 mutation) .Median time to progression was 14 months and did not differ based on EGFR mutation status. Toxicity was acceptable no grade 5 toxicity, I grade 4, and 11 grade 3). Twelve (26%) had complete responses ( 10 with wild type (wt) and 2 with mutation (mt)and 1 unknown).At 73.5 months median follow-up (range 46.2 - 93.7months), 2 and 5 year OS rates were 67.4 % and 36.25%, although there were no significant difference by mutation status. Twelve patients had no progression and 34 had local and/or distant metastasis. All 4 patients with EGFR mutation had local control. Eleven of 27 patients failed in the brain (7 wt, 3 mt and I unkown). Toxicity was acceptable and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy. Those patients with EGFR mutation might need induction erlotinib followed by local treatment when they will fail locally in the lung or brain metastasis which is fairly frequent among EGFR mutated patients.