Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors

George D. Demetri, Filippo De Braud, Alexander Drilon, Salvatore Siena, Manish R. Patel, Byoung Chul Cho, Stephen V. Liu, Myung Ju Ahn, Chao Hua Chiu, Jessica J. Lin, Koichi Goto, Jeeyun Lee, Lyudmila Bazhenova, Thomas John, Marwan Fakih, Sant P. Chawla, Rafal Dziadziuszko, Takashi Seto, Sebastian Heinzmann, Bethany PitcherDavid Chen, Timothy R. Wilson, Christian Rolfo

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13 引文 斯高帕斯(Scopus)


Purpose: Entrectinib potently inhibits tropomyosin receptor kinases (TRKAs)/B/C and ROS1, and previously induced deep [objective response rate (ORR) 57.4%] and durable [median duration of response (DoR) 10.4 months] responses in adults with NTRK fusion-positive solid tumors from three phase I/II trials. This article expands prior reports with additional patients and longer follow-up. Patients and Methods: Patients with locally advanced/metastatic NTRK fusion-positive solid tumors and ≥12 months' follow-up were included. Primary endpoints were ORR and DoR by blinded independent central review (BICR); secondary endpoints included progression-free survival (PFS), intracranial efficacy, and safety. The safety-evaluable populations included all patients who had received ≥1 entrectinib dose. Results: At clinical cut-off (August 31, 2020), the efficacyevaluable population comprised 121 adults with 14 tumor types and ≥30 histologies. Median follow-up was 25.8 months; 61.2% of patients had a complete (n = 19) or partial response (n = 55). Median DoR was 20.0 months [95% confidence interval (CI), 13.0- 38.2]; median PFS was 13.8 months (95% CI, 10.1-19.9). In 11 patients with BICR-assessed measurable central nervous system (CNS) disease, intracranial ORR was 63.6% (95% CI, 30.8-89.1) and median intracranial DoR was 22.1 (95% CI, 7.4-not estimable) months. The safety profile of entrectinib in adults and pediatric patients was aligned with previous reports. Most treatment-related adverse events (TRAEs) were grade 1/2 and manageable/reversible with dose modifications. TRAE-related discontinuations occurred in 8.3% of patients. Conclusions: With additional clinical experience, entrectinib continues to demonstrate durable systemic and intracranial responses and can address the unmet need of a CNS-active treatment in patients with NTRK fusion-positive solid tumors.
頁(從 - 到)1302-1312
期刊Clinical Cancer Research
出版狀態已發佈 - 4月 2022

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究


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