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

Po Lan Su, Jeng Shiuan Tsai, Szu Chun Yang, Yi Lin Wu, Yau Lin Tseng, Chao Chun Chang, Yi Ting Yen, Chia Ying Lin, Chien Chung Lin, Chin Chou Wang, Meng Chih Lin, Wu Chou Su

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Objectives: 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. Material and methods: 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. Results: 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 <1) between AZD9291 and chemotherapy and a higher proportion of apoptosis cells in combination treatment were also demonstrated in the T790M-positive PC9 cell line with acquired resistance to AZD9291. Conclusion: Our data supported the hypothesis that osimertinib-based combination therapy is associated with improved OS among patients with clinical progression following the use of osimertinib. These findings warrant further validation in a randomised controlled study.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalLung Cancer
Volume158
DOIs
Publication statusPublished - 2021 Aug

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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