Larotrectinib in patients with tropomyosin receptor kinase fusion solid tumors in Spain (SPAINTRK).

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.