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

Demetri, GD; de Braud, F; Drilon, A; Siena, S; Patel, MR; Cho, BC; Liu, SV; Ahn, MJ; Chiu, CH; Lin, JJ; Goto, K; Lee, J; Bazhenova, L; John, T; Fakih, M; Chawla, SP; Dziadziuszko, R; Seto, T; Heinzmann, S; Pitcher, B; Chen, D; Wilson, TR; Rolfo, C

Author(s): Demetri, GD; de Braud, F; Drilon, A; Siena, S; Patel, MR; Cho, BC; Liu, SV; Ahn, MJ; Chiu, CH; Lin, JJ; Goto, K; Lee, J; Bazhenova, L; John, T; Fakih, M; Chawla, SP; Dziadziuszko, R; Seto, T; Heinzmann, S; Pitcher, B; Chen, D; Wilson, TR; Rolfo, C;
Details: Publication Year 2022-04-01,Volume 28,Issue #7,Page 1302-1312
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: 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 efficacy-evaluable 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.
Keywords: Adult; Benzamides; *Carcinoma, Non-Small-Cell Lung/drug therapy; Child; Humans; Indazoles; *Lung Neoplasms/drug therapy; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
Department(s): Medical Oncology
PubMed ID: 35144967
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-21-3597
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-21-3597
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-23 06:31:29

Last Modified: 2024-10-23 06:33:16