Real-world outcomes of larotrectinib in solid tumors with tropomyosin receptor kinase fusion (GETNE S2411/SPAINTRK).

Abstract

e23344 Background: NTRK gene fusions have been described as oncogenic drivers in diverse adult and paediatric cancers, as they promote cell survival and proliferation. Larotrectinib is a first-in-class TRK inhibitor with proven activity in a broad range of solid tumors. This study aimed to describe the effectiveness of larotrectinib in patients with solid tumors harbouring NTRK fusions in Spain. Methods: SPAINTRK is an observational, retrospective study that included adult and paediatric patients with a confirmed diagnosis of solid neoplasms bearing NTRK fusions. All patients were treated with larotrectinib in the context of the compassionate drug use program between EMA approval and commercialisation in Spain (October 2019 – September 2023). Patients treated with larotrectinib in clinical trials were excluded. NTRK fusions were detected using NGS, FISH, and/or IHC, along with confirmatory molecular test. The primary endpoint was to determine the effectiveness of larotrectinib using Duration of Response (DoR). The secondary endpoints were objective response rate (ORR) and safety. Results: Between February and June 2025, 20 patients from ten months to 81 years were included, 15 adults and 5 paediatrics. Eight different solid tumor types with NTRK fusions were represented. NTRK fusions were reported in NTRK1 gene (40%), NTRK2 (25%) and NTRK3 (35%), 65% of patients were diagnosed using NGS. Larotrectinib was administered for a median of 13 months (95% CI: 8-21). 45% of patients received larotrectinib as first-line treatment while 55% had received previous treatments. After a median follow-up of 24.4 months (95% CI: 13.2-35), the median DoR was 24.5 months (95% CI: 11.1- not reached) and ORR was 60% (95% CI: 36.1-80.9). ORR was higher among pediatric patients (80%; 95% CI: 28.4-99.5). The highest ORR were seen among patients with infant fibrosarcoma (100%; 95% CI: 29.2-100) and lung tumors (80%; 95% CI: 28.44-99.5). After 1 year of treatment, 60% of patients remained progression-free and 75% of the patients who showed response maintained it. At data cutoff, 41.7% of the patients with a response were disease-free and/or remained on treatment. Treatment-related AEs were uncommon, with neutropenia and transaminitis being the most frequent, reported in up to 15% of patients each. Conclusions: Larotrectinib evoked long antitumor responses in solid tumours with NTRK fusion in the real world, regardless of the tumor type. No safety concerns were reported, even after long-term administration. Screening techniques such as NGS should be implemented, and although its use is increasing, broader access is required. Clinical trial information: NCT06837090 .