Efficacy and safety of larotrectinib in patients with TRK fusion lung cancer: An updated analysis.

8610 Background: NTRK gene fusions are oncogenic drivers in various tumor types, including lung cancer. Larotrectinib is the first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumor-agnostic use in patients with TRK fusion cancer based on a robust and durable objective response rate in patients with various cancers. Here, we report updated long-term efficacy and safety data in the subset of patients with TRK fusion lung cancer treated with larotrectinib. Methods: Patients with TRK fusion lung cancer enrolled in 2 larotrectinib clinical trials (NCT02122913, NCT02576431) were included. Larotrectinib was administered at 100 mg twice daily. Responses were independent review committee-assessed per Response Evaluation Criteria in Solid Tumours version 1.1. The data cutoff was July 20, 2024. Results: At data cutoff, 32 patients were enrolled; 12 patients had known CNS metastases at baseline. The median age was 56 years (range 25–81). One patient (3%) was systemic treatment-naïve in the metastatic/unresectable setting, and 19 (59%) patients received 2 or more prior therapies. All NTRK gene fusions were identified by next-generation sequencing (NGS). The overall response rate was 69% (95% confidence interval [CI] 50–84): 4 (13%) complete responses, 18 (56%) partial responses, 6 (19%) stable disease, 2 (6%) progressive disease, and 2 (6%) not evaluable. Median time to response was 1.8 months (range 1.5–7.3). Median duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were 34 months (95% CI 13–not estimable [NE]), 22 months (95% CI 10–39), and 41 months (95% CI 17−NE), respectively, at median follow-ups of 37, 38, and 46 months. The 4-year rates for DoR, PFS, and OS were 33% (95% CI 7–60), 26% (95% CI 6–45), and 48% (95% CI 29–68), respectively. The median duration of treatment was 20 months (range 2–75). At data cutoff, 8 (25%) patients remained on treatment: 7 had responded and 1 was not evaluable for response. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. Grade 3/4 TRAEs were reported in 10 (31%) patients. One (3%) patient discontinued treatment due to TRAEs (increased alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase). Conclusions: Larotrectinib demonstrates rapid and durable responses, extended survival, clinical benefit, and a favorable safety profile in patients with advanced TRK fusion lung cancer. These results support the wider adoption of NGS panels that include NTRK gene fusions in patients with lung cancer to identify those who may benefit from targeted treatment. Clinical trial information: NCT02122913 , NCT02576431 .