Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer

Rafal Dziadziuszko, Matthew G. Krebs, Filippo De Braud, Salvatore Siena, Alexander Drilon, Robert C. Doebele, Manish R. Patel, Byoung Chul Cho, Stephen V. Liu, Myung-Ju Ahn, Chao-Hua Chiu, Anna F. Farago, Chia-Chi Lin, Christos S. Karapetis, Yu-Chung Li, Bann-Mo Day, David Chen, Timothy R. Wilson, Fabrice Barlesi

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    PURPOSE Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1) are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in ROS1 fusion–positive NSCLC. METHODS The efficacy-evaluable population included adults with locally advanced or metastatic ROS1 fusion–positive NSCLC with or without CNS metastases who received entrectinib $ 600 mg orally once per day. Co-primary end points were objective response rate (ORR) assessed by blinded independent central review and duration of response (DoR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety. RESULTS In total, 161 patients with a follow-up of $ 6 months were evaluable. The median treatment duration was 10.7 months (IQR, 6.4-17.7). The ORR was 67.1% (n 5 108, 95% CI, 59.3 to 74.3), and responses were durable (12-month DoR rate, 63%, median DoR 15.7 months). The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81% (median OS not estimable). In 24 patients with measurable baseline CNS metastases by blinded independent central review, the intracranial ORR was 79.2% (n 5 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (12-month rate, 55%). The safety profile in this updated analysis was similar to that reported in the primary analysis, and no new safety signals were found. CONCLUSION Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion–positive NSCLC, including patients with CNS metastases.

    Original languageEnglish
    Pages (from-to)1253-1263
    Number of pages13
    JournalJournal of Clinical Oncology
    Issue number11
    Publication statusPublished - 10 Apr 2021


    • Entrectinib
    • Metastatic ROS1
    • Lung Cancer
    • non-small-cell lung cancer
    • ROS1 tyrosine kinase inhibitor
    • ROS1 fusion–positive NSCLC
    • NSCLC


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