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.
Keywords: Acquired resistance; EGFR-tyrosine kinase inhibitors; TS-1; non-small cell lung cancer; phase II study.
© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.