Larotrectinib in patients with tropomyosin receptor kinase fusion solid tumors in Spain (SPAINTRK)
Jorge Hernando1, Carlos Lopez2, Alejandro Garcia-Alvarez1
1Department of Medical Oncology, Hepatobiliary Pancreatic Cancer and Endocrine Tumors, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Neuroendocrine and Endocrine Tumor Translational Research Program (NET-VHIO), Vall Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Background:
Larotrectinib is a first-in-class, selective tropomyosin receptor kinase (TRK) inhibitor with proven activity across solid tumors. This study aimed to describe larotrectinib's effectiveness in patients with solid tumors in Spain.
Methods:
SPAINTRK (NCT06837090) was a retrospective study including adult and pediatric patients with solid neoplasms treated with larotrectinib through compassionate use, between European Medicines Agency (EMA) approval and commercialization in Spain. TRK fusions were determined as part of standard care using next-generation sequencing (NGS), fluorescence in situ hybridization, or immunohistochemistry plus a confirmatory molecular test. The primary endpoint was duration of response (DoR). No formal sample size was calculated.
Results:
From February to June 2025, 20 patients aged ten months to 81 years were included. Eight solid tumor types with TRK fusions were included involving NTRK1 gene in 8 patients (40 %), NTRK2 in 5 (25 %), and NTRK3 in 7 (35 %). NGS was used in 65 %. Median DoR was 24.5 months (95 % CI: 11.1- not reached) and objective response rate was 60 % (95 % CI: 36.1-80.9). At one year, 75 % of responses (9 out of 12) were ongoing, and 12 patients (60 %) remained progression-free. At data cutoff (median follow-up of 24.4 months (95 % CI: 13.2-35)), 41.7 % of the patients with a response were disease-free and/or remained on treatment. Treatment-related neutropenia and transaminitis were reported in 15 % of patients each.
Conclusions:
Larotrectinib evoked broad and durable antitumor activity in a plethora of solid tumors with NTRK fusions. Safety profile was consistent with that of clinical trials, even after long-term administration. While NGS use is increasing, broader access is needed.
Insights
Larotrectinib demonstrated significant effectiveness in treating various solid tumors with NTRK fusions in Spain. The tropomyosin receptor kinase (TRK) inhibitor showed durable responses and a manageable safety profile in patients.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor with established efficacy in solid tumors.
- This study evaluated larotrectinib's effectiveness in Spanish patients with solid tumors harboring TRK fusions.
Purpose of the Study:
- To describe the effectiveness of larotrectinib in patients with solid tumors in Spain.
- To assess the duration of response and safety of larotrectinib in a real-world setting.
Main Methods:
- Retrospective SPAINTRK study (NCT06837090) of adult and pediatric patients treated with larotrectinib via compassionate use.
- TRK fusions identified using next-generation sequencing (NGS), fluorescence in situ hybridization, or immunohistochemistry.
- Primary endpoint: duration of response (DoR).
Main Results:
- Twenty patients with eight solid tumor types and TRK fusions were included.
- Median DoR was 24.5 months; objective response rate was 60%.
- Seventy-five percent of responses were ongoing at one year; 60% remained progression-free.
Conclusions:
- Larotrectinib exhibited broad and durable antitumor activity in diverse solid tumors with NTRK fusions.
- The safety profile was consistent with prior clinical trials, even with long-term use.
- Increased access to next-generation sequencing (NGS) is recommended for broader patient identification.
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