Dr Subbiah on Outcomes With Larotrectinib in TRK Fusion–Positive Solid Tumors

Vivek Subbiah, MD, chief, Early-Phase Drug Development, Sarah Cannon Research Institute, discusses key data from the observational VICTORIA study (NCT05192642) which evaluated treatment with the highly selective TRK inhibitor larotrectinib in patients with solid tumors harboring TRK gene fusions.

VICTORIA was a protocol-driven, exact-matching study in which the outcomes of patients with TRK fusion–positive cancer who received larotrectinib across 3 clinical trials (NCT02122913; NCT02576431;NCT02637687) were compared with outcomes for real-world patients treated with non–TRK inhibitor or standard-of-care therapies. The study comprised patients with tumor types such as non–small cell lung cancer, colorectal cancer, thyroid cancer, soft tissue sarcomas, and salivary gland carcinoma. Patients were required to have advanced stage or metastatic disease.

Results from VICTORIA presented at the 2024 ASCO Annual Meeting showed thattreatment with larotrectinib was associated with longer overall survival (OS) and all measured time-to-event end points among patients with TRK fusion–positive cancers vs standard non-TRK inhibitor therapies, Subbiah reports. The median OS with larotrectinib was not reached, whereas patients receiving non–TRK inhibitor therapies had a median OS of 37.2 months (HR, 0.44; 95% CI, 0.23-0.83). The median duration of therapy (DOT) was 30.8 months for larotrectinib vs 3.4 months for non–TRK inhibitor therapies (HR, 0.23; 95% CI, 0.15-0.33); time to next treatment (TTNT) was not reached vs 10.6 months for these respective groups (HR, 0.22; 95% CI, 0.13-0.38). Additionally, the median progression-free survival (PFS) was 36.8 months with larotrectinib compared with 5.2 months with standard therapies (HR, 0.29; 95% CI, 0.18-0.46). Results in unweighted analyses were consistent with weighted analyses for DOT, TTNT and PFS.

Response rates were also higher in patients treated with larotrectinib, although exact figures were impacted by the tumor type composition and missing response data in the real-world cohort, Subbiah adds. These findings reinforce the substantial benefit of larotrectinib for TRK fusion–positive cancers, highlighting its benefit over traditional treatments, he says. They also support the broader implementation of next-generation sequencing panels to detect TRK gene fusions, facilitating earlier identification and treatment of patients who could benefit from targeted therapies, Subbiah concludes.