Clinical outcomes of platinum-based chemotherapy according to T790M mutation status in EGFR-positive non-small cell lung cancer patients after initial EGFR-TKI failure

Abstract

BackgroundEmergence of the T790M point mutation in exon 20 of epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). It remains unclear whether the efficacy of platinum-doublet chemotherapy is impacted by the presence of the T790M mutation. The aim of this study is to evaluate the efficacy of platinum-doublet chemotherapy after initial EGFR-TKI failure according to the EGFR T790M in patients with advanced EGFR-mutation-positive non-small cell lung cancer (NSCLC). Patients and methodsWe retrospectively reviewed 50 patients with advanced NSCLC harboring EGFR mutations who underwent rebiopsy to evaluate their T790M mutation status after development of resistance to first-line EGFR-TKIs (gefitinib, erlotinib, or afatinib) and were subsequently treated with second-line platinum-based chemotherapy. ResultsThe median age of patients was 63 years (range, 35–77 years), and 15 (30%) patients were male. Histological examination revealed that all patients had adenocarcinoma, 39 (78%) had stage IV disease, and 11 (22%) patients had postoperative recurrence. Of all, 17 patients (34%) had the T790M mutation by rebiopsy after initial EGFR-TKI failure. The overall response rate (ORR) of platinum-doublet chemotherapy was 24% for both T790M-positive and T790M-negative patients. There was no significant difference in the progression-free survival (PFS) in T790M-positive and T790M-negative patients (median PFS, 6.0 months vs. 5.1 months; 95% confidence interval [CI], 0.1–11.9 vs. 4.4–5.8; hazard ratio [HR], 0.90 [95%CI, 0.49–1.66]; P=0.7210). None of the factors were predictive of platinum-doublet chemotherapy efficacy by the multivariate analysis. ConclusionThere were no differences in clinical outcomes of platinum-based chemotherapy according to the T790M status of NSCLC patients.