Results of larotinib/larlotinib in the treatment of TRK fusion-positive solid tumors

The Sarah Cannon Institute for Early Medicine discusses key data from the observational VICTORIA study (NCT05192642), which evaluated the highly selective TRK inhibitor larotrectinib in patients with TRK gene fusion solid tumors.

VICTORIA is a protocol-driven exact-match study in which outcomes in patients with TRK fusion-positive cancers treated with larotrectinib in 3 clinical trials (NCT02122913; NCT02576431; NCT02637687) were compared with real-world outcomes in patients treated with non-TRK inhibitors or standard of care. The study included patients with tumor types including non-small cell lung cancer, colorectal cancer, thyroid cancer, soft tissue sarcoma and salivary gland cancer. Patients were required to have advanced or metastatic disease.

Results from VICTORIA presented at the 2024 ASCO Annual Meeting show that treatment with larotrectinib is associated with longer overall survival (OS) and all measured time-event endpoints compared with standard non-TRK inhibitor treatment in patients with TRK fusion-positive cancers. Median OS was not reached with larotrectinib and was 37.2 months for patients treated with non-TRK inhibitors (HR, 0.44; 95% CI, 0.23-0.83). The median duration of treatment with larotrectinib was 30.8 months compared with 3.4 months with non-TRK inhibitor treatment (HR, 0.23; 95% CI, 0.15-0.33); time to next treatment not reached (TTNT) was compared with 10.6 months in these groups (HR, 0.22; 95% CI, 0.13-0.38). In addition, the median progression-free survival (PFS) was 36.8 months in the larotrectinib group compared with 5.2 months in the standard-therapy group (HR, 0.29; 95% CI, 0.18-0.46). The results of the unweighted analysis are consistent with the weighted analysis of DOT, TTNT and PFS.

Response rates were also higher in patients treated with larotrectinib, although the exact numbers are affected by tumor type composition and missing response data in the real-world cohort. He said these findings reinforce the substantial benefit of larotrectinib in TRK fusion-positive cancers and highlight its benefits over conventional treatments. They also support broader implementation of next-generation sequencing panels to detect TRK gene fusions, facilitating early identification and treatment of patients who may benefit from targeted therapies.

Reference materials:https://www.onclive.com/view/dr-subbiah-on-outcomes-with-larotrectinib-in-trk-fusion-positive-solid-tumors