Survival benefit of osimertinib combination therapy in patients with T790M-positive non-small-cell lung cancer refractory to osimertinib treatment

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2021-08, Vol.158, p.137-145
• Main Authors: Su, Po-Lan, Tsai, Jeng-Shiuan, Yang, Szu-Chun, Wu, Yi-Lin, Tseng, Yau-Lin, Chang, Chao-Chun, Yen, Yi-Ting, Lin, Chia-Ying, Lin, Chien-Chung, Wang, Chin-Chou, Lin, Meng-Chih, Su, Wu-Chou
• Format: Article
• Language: English
• Subjects: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Combination therapy; ErbB Receptors - genetics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Mutation; Osimertinib resistance; Protein Kinase Inhibitors - therapeutic use; T790M mutation
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2021.06.014

•The IMPRESS study demonstrated that continuation of gefitinib in combination with cisplatin and pemetrexed had no clinical benefits.•However, no previous studies assessed the continuation of osimertinib in EGFR T790M NSCLC patients after disease progression.•Osimertinib-based combination therapy provides better post-progression survival in T790M-positive NSCLC patient resistant to osimertinib.•In vitro study confirmed the synergism between chemotherapy and osimertinib. Osimertinib is the main treatment choice for pretreated patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) T790M mutations. However, the choice of subsequent therapy when progressive disease has developed after osimertinib treatment remains a major therapeutic challenge. This study evaluated the efficacy of osimertinib-based combination therapies in patients who developed progressive disease after treatment with osimertinib. We enrolled NSCLC patients harbouring T790M mutations pretreated with first- or second-generation EGFR tyrosine-kinase inhibitors and were receiving osimertinib at two tertiary referral centres between August 2015 and July 2019, and the subsequent treatment efficacy was assessed. Osimertinib-based combination therapy yielded better overall survival (OS) than chemotherapy alone (not achieved vs. 7.8 months; hazard ratio, 0.39; 95 % confidence interval 0.17–0.89; P = 0.025) according to the Cox proportional hazards model adjusted for possible confounders. Synergism (combination index