1289P Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in a range of tumour types. Larotrectinib, a central nervous system (CNS)-active and highly selective EMA- and FDA-approved TRK inhibitor, demonstrated an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 months across multiple cancers (Hong et al. Lancet Oncol 2020). We report updated data on patients with lung cancer treated with larotrectinib. Patients with lung cancer harbouring an NTRK gene fusion enrolled in two clinical trials were pooled for this analysis. Larotrectinib 100 mg BID was administered on a continuous 28-day schedule. Response was assessed by the investigator per RECIST v1.1. As of 15 July 2019, 14 patients with metastatic TRK fusion lung cancer were enrolled: 13 with non-small cell lung cancer and 1 with small cell lung cancer. The median age was 52 years (range 25–76). Eleven patients had fusions involving NTRK1 and three patients had fusions involving NTRK3. Seven patients had baseline CNS metastases. Patients were heavily pre-treated with a median of three prior therapies (range 1–5); nine patients had received ≥2 prior therapies. The ORR with larotrectinib was 71% (95% CI 42–92%): one patient had a complete response, nine had partial responses, three had stable disease and one had progressive disease. The ORR in patients with CNS metastases was 57% (95% CI 18–90). The overall DoR ranged from 1.9+ to 28.7+ months. The median progression-free survival (PFS) had not been reached (range 1.8–30.3+ months), with an estimated PFS rate at 12 months of 69%. Treatment duration ranged from 2.1 to 39.6+ months. Larotrectinib was well tolerated, with treatment-emergent adverse events being mainly grade 1–2. In this updated analysis, larotrectinib was shown to be highly active in patients with advanced lung cancer harbouring NTRK gene fusions, including those with CNS metastases. The drug has a favourable safety profile. These results support inclusion of NTRK gene fusions in routine molecular testing of patients with lung cancer.