Tatsuya Yoshida1, Hiroaki Kuroda2, Yuko Oya3, Junichi Shimizu3, Yoshitsugu Horio3, Yukinori Sakao2, Toyoaki Hida3, Yasushi Yatabe4. 1. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan. Electronic address: t.yoshida@aichi-cc.jp. 2. Department of Thoracic Surgery, Aichi Cancer Center Hospital, Aichi, Japan. 3. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan. 4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, Japan.
Abstract
BACKGROUND: Emergence 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 METHODS: We 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. RESULTS: The 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. CONCLUSION: There were no differences in clinical outcomes of platinum-based chemotherapy according to the T790M status of NSCLC patients.
BACKGROUND: Emergence 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 EGFRT790M in patients with advanced EGFR-mutation-positive non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We 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. RESULTS: The 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. CONCLUSION: There were no differences in clinical outcomes of platinum-based chemotherapy according to the T790M status of NSCLCpatients.