Larotrectinib Delivers 53% ORR—and 83% in Secretory Subtype—with 73% 4-Year Durability in TRK-Fusion Breast Cancer

Larotrectinib, a highly selective CNS-penetrant TRK inhibitor, was evaluated across NAVIGATE and SCOUT (n = 16; TRK-fusion breast cancer). Notably, NTRK fusions are rare in breast cancer (0.4%) but are present in 90% of secretory carcinomas (Dietrich et al., 2025). Among IRC-evaluable patients (n = 15), ORR reached 53% (27% CR), rising to 83% in secretory carcinoma (n = 6; 38%), with responses in both TNBC and ER+ disease. Median time-to-response was 1.7 mo; median duration of response was not reached, and the 4-year DOR, PFS, and OS rates were 73%, 38%, and 38%, respectively. Median PFS was 9 mo and median OS 21 mo after 44–47 mo follow-up. Grade 3/4 TRAEs (19%) were limited to reversible hepatic events, paresthesia, and thrombocytopenia, with no treatment-related discontinuations. By comparison, single-agent capecitabine in pretreated metastatic breast cancer achieves ~20% ORR and ~4 mo PFS, underscoring larotrectinib’s potency and durability even in heavily pretreated settings.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P4-08-29/752349/Abstract-P4-08-29-Efficacy-and-safety-of