KEY TAKEAWAYS
- The STARTRK-1 trial Phase I/II, registered under NCT02097810, aimed to assess the efficacy and safety of entrectinib in treating patients with locally advanced/metastatic NTRK fusion-positive solid tumors.
- Patients with NTRK fusion-positive solid tumors and ≥12 months’ follow-up were included in the study.
- The study concluded that entrectinib continues to demonstrate durable systemic and intracranial responses and can address the unmet need for a CNS-active treatment in patients with NTRK fusion-positive solid tumors.
Entrectinib is a potent inhibitor of tropomyosin receptor kinases (TRKAs/B/C) and ROS1 and has previously shown promising results in treating neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors. The study presented new data with additional patients and more extended follow-up periods. It included patients with advanced NTRK fusion-positive tumors, and the primary endpoints were the objective response rate (ORR) and duration of response (DoR), as determined by blinded independent central review (BICR). Progression-free survival (PFS), intracranial effectiveness, and safety were secondary objectives. All patients who had received at least one dose of entrectinib were included in the safety evaluation. As of the clinical cut-off date of August 31, 2020, the study evaluated 121 adults with 14 different types of tumors and ≥30 histologies. The median follow-up period was 25.8 months, and 61.2% of patients had a partial or complete response to treatment (n=55 and n=19, respectively). The median duration of response was 20.0 months (95% confidence interval (CI), 13.0-38.2), and the median progression-free survival (PFS) was 13.8 months (95% CI, 10.1-19.9).
Of the 11 patients with BICR-assessed measurable central nervous system (CNS) disease, the intracranial objective response rate (ORR) was 63.6% (95% CI, 30.8-89.1), and the median intracranial duration of response was 22.1 months (95% CI, 7.4-not estimable). Entrectinib’s safety profile was consistent with earlier findings in adult and pediatric patients, with most treatment-related adverse events (TRAEs) being grade 1/2 and treatable with dose adjustments. Treatment-related adverse event-related discontinuations occurred in 8.3% of patients. The study revealed that entrectinib had shown persistent systemic and intracranial responses, indicating its efficacy as a treatment option for NTRK fusion-positive solid tumors with a need for CNS-active therapy.
Source: https://pubmed.ncbi.nlm.nih.gov/35144967/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02097810/
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. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors. Clin Cancer Res. 2022 Apr 1;28(7):1302-1312. doi: 10.1158/1078-0432.CCR-21-3597. Erratum in: Clin Cancer Res. 2022 May 13;28(10):2196. PMID: 35144967; PMCID: PMC9365368.
