Combination TS‐1 plus EGFR‐tyrosine kinase inhibitors (TKIs) for the treatment of non‐small cell lung cancer after progression on first‐line or further EGFR‐TKIs: A phase II, single‐arm trial

BACKGROUND: EGFR‐tyrosine kinase inhibitors (TKIs) combined with TS‐1 might overcome EGFR‐TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR‐TKIs and TS‐1 in non‐small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR‐TKI therapy. METHODS: This was a phase II, single‐arm and single‐center prospective study. Stage IIIB–IV NSCLC patients with acquired resistance to prior EGFR‐TKI treatment were enrolled. All patients were administered combination therapy of TS‐1 and continuing EGFR‐TKIs in this study. The primary endpoints were progression‐free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. RESULTS: A total of 42 patients with acquired resistance to EGFR‐TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6–5.4). The OS and DCR were 31.9 (95% CI 17.8–46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. CONCLUSION: The combination treatment of TS‐1 and EGFR‐TKIs was effective and well tolerated by patients who had experienced prior EGFR‐TKI treatment failure. Our results need to be validated by larger prospective clinical trials.