| Autor: |
Christian Rolfo, Timothy R. Wilson, David Chen, Bethany Pitcher, Sebastian Heinzmann, Takashi Seto, Rafal Dziadziuszko, Sant P. Chawla, Marwan Fakih, Thomas John, Lyudmila Bazhenova, Jeeyun Lee, Koichi Goto, Jessica J. Lin, Chao-Hua Chiu, Myung-Ju Ahn, Stephen V. Liu, Byoung Chul Cho, Manish R. Patel, Salvatore Siena, Alexander Drilon, Filippo De Braud, George D. Demetri |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6532467 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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