A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling
- Author(s)
- Thavaneswaran, S; Sim, HW; Grady, J; Espinoza, D; Huang, ML; Lin, F; McGrath, M; Desai, J; Charakidis, M; Brown, M; Kansara, M; Simes, J; Thomas, D;
- Journal Title
- Oncologist
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear. METHODS: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type. The primary endpoint was objective response rate (ORR), with secondary endpoints including time-to-progression (TTP) ratio [TTP on study to TTP on previous systemic therapy (TTP1)], progression-free survival (PFS), and overall survival (OS). Initially planned for 2 non-comparator groups: primary central nervous system (CNS) and non-CNS tumours with NTRK fusions, the protocol was amended to permit NTRK overexpression. RESULTS: Seventeen patients were treated with larotrectinib: one glioblastoma with a SPECC1L::NTRK2 fusion (group 1), and a peripheral nerve sheath tumor with a TPM3::NTRK1 fusion and 15 patients with overexpression (group 2). The ORR was 6%. An additional 3 of 12 (25%) TTP1-evaluable patients achieved a TTP ratio ≥1.3 and 2 of 5 without an evaluable TTP1 had a PFS >6 months. Median PFS and OS were 3.5 (95% CI, 1.4-6.0) and 15.9 months (95% CI, 6.4-NR), respectively. CONCLUSION: Unlike its efficacy in NTRK-fusion positive cancers, larotrectinib did not demonstrate a signal of efficacy among tumors with NTRK overexpression.
- Keywords
- NTRK fusions; NTRK overexpression; TRK inhibitor; larotrectinib
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1093/oncolo/oyae339
- Open Access at Publisher's Site
https://doi.org/10.1093/oncolo/oyae339- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-23 02:18:56
Last Modified: 2025-01-23 02:30:24