Patients treated with platinum-doublet chemotherapy for advanced non--small-cell lung cancer have inferior outcomes if previously treated with platinum-based chemoradiation

Abstract

Introduction: The standard of care for locoregionally advanced non-small-cell lung cancer is concurrent platinum-based chemoradiation. Many patients relapse, and subsequent systemic treatment may involve platinum-doublet chemotherapy. It is not known if prior platinum-based chemoradiation influences the response to platinum-based chemotherapy given subsequently for relapse. Therefore, we compared outcomes in these patients with those in patients without prior treatment.

Methods: A retrospective study of patients who had been treated with carboplatin and gemcitabine chemotherapy for de novo metastatic disease or recurrent non--small-cell lung cancer after receiving platinum-based chemoradiation. The primary outcome was progression-free survival (PFS).

Results: A total of 104 patients were analyzed. The median age was 63 years (range, 35-81 years), with 63 (61%) patients with newly diagnosed disease and with 41 (39%) who were previously treated. The response rate was significantly lower for those previously exposed to chemoradiation (10% vs. 29%: P = .001), as was the median PFS (3.6 months vs. 5.7 months; P = .002), and median overall survival (OS) (8.6 months vs. 12.1 months; P = .007). Only the treatment group was a significant predictor (P = .032) of PFS by univariate analysis. In univariate analysis; sex (men; P = .04), histology (squamous cell; P = .04), Eastern Cooperative Oncology Group Performance Status Scale (P = .002), and treatment group (P = .023) predicted significantly inferior OS. Multivariate analysis showed that performance status was the only significant predictor of inferior OS.

Conclusion: Outcomes were inferior in patients previously exposed to platinum-based chemoradiation. An approach of stratifying such patients in future trials of chemotherapy should be adopted. Alternative options such as non--platinum-based agents or targeted therapies should be considered in this group.

Keywords: Chemoradiation; Non–small-cell lung cancer; Platinum resistance.