Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion–Positive NSCLC

Alexander Drilon, Chao Hua Chiu, Yun Fan, Byoung Chul Cho, Shun Lu, Myung Ju Ahn, Matthew G. Krebs, Stephen V. Liu, Thomas John, Gregory A. Otterson, Daniel S.W. Tan, Tejas Patil, Rafal Dziadziuszko, Erminia Massarelli, Takashi Seto, Robert C. Doebele, Bethany Pitcher, Nino Kurtsikidze, Sebastian Heinzmann, Salvatore Siena

Research output: Contribution to journalArticlepeer-review


Introduction: Entrectinib is an approved tyrosine kinase inhibitor (TKI) for ROS1 fusion–positive NSCLC. An updated integrated analysis of entrectinib from the ALKA-372-001, STARTRK-1, and STARTRK-2 trials is presented, with substantially longer follow-up, more patients, and the first description of the median overall survival (OS). An exploratory analysis of entrectinib in ROS1 fusion–positive NSCLC with the central nervous system (CNS)–only progression post-crizotinib is reported. Methods: Adults with ROS1 fusion–positive, locally advanced or metastatic NSCLC who received at least one dose of entrectinib and had 12 months or longer of follow-up were included in the analysis. Co-primary end points were confirmed objective response rate (ORR) and duration of response (DoR) by blinded independent central review. The data cutoff was on August 31, 2020. Results: The efficacy-assessable population comprised 168 ROS1 TKI–naïve patients. The median survival follow-up was 29.1 months (interquartile range, 21.8–35.9). The ORR was 68% (95% confidence interval [CI]: 60.2–74.8); the median DoR was 20.5 months. The median progression-free survival (PFS) was 15.7 months and the median OS was 47.8 months. In the 25 patients with measurable baseline CNS metastases, the intracranial ORR was 80% (95% CI: 59.3–93.2), median intracranial DoR was 12.9 months, and median intracranial PFS was 8.8 months. Among 18 patients with CNS-only progression on previous crizotinib treatment, two achieved a partial response (11%) and four had stable disease (22%). In seven patients with measurable CNS disease from this cohort, the intracranial ORR was 14% (1 partial response). Conclusions: Entrectinib is active and achieves prolonged survival in ROS1 TKI–naïve patients with ROS1 fusion–positive NSCLC. Modest activity is seen in patients with CNS-only progression post-crizotinib.
Original languageEnglish
JournalJTO Clinical and Research Reports
Issue number6
Publication statusPublished - 2022


  • Entrectinib
  • Intracranial efficacy
  • ROS1 fusions
  • Treatment post-crizotinib


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