1. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid TumorsEntrectinib in NTRK+ Solid Tumors: Updated Efficacy/Safety
- Author
-
Demetri, George D, De Braud, Filippo, Drilon, Alexander, Siena, Salvatore, Patel, Manish R, Cho, Byoung Chul, Liu, Stephen V, Ahn, Myung-Ju, Chiu, Chao-Hua, Lin, Jessica J, Goto, Koichi, Lee, Jeeyun, Bazhenova, Lyudmila, John, Thomas, Fakih, Marwan, Chawla, Sant P, Dziadziuszko, Rafal, Seto, Takashi, Heinzmann, Sebastian, Pitcher, Bethany, Chen, David, Wilson, Timothy R, and Rolfo, Christian
- Subjects
Cancer ,Clinical Trials and Supportive Activities ,Brain Disorders ,Neurosciences ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Benzamides ,Carcinoma ,Non-Small-Cell Lung ,Child ,Humans ,Indazoles ,Lung Neoplasms ,Protein-Tyrosine Kinases ,Proto-Oncogene Proteins ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeEntrectinib 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 methodsPatients 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.ResultsAt 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.ConclusionsWith 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.
- Published
- 2022