Sub-group analyses of 3 Vitrakvi post-hoc studies in TRK fusion cancer presented at ASCO.- Bayer

Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer (Abstract 3141). In post-hoc subgroup analyses (data cut-off July 2022) of adult patients (n=180) with TRK fusion cancer across 24 different tumor types, including patients with central nervous system (CNS) metastases (n=22), Vitrakvi demonstrated an objective response rate (ORR) of 57% (95% CI 50-65) {16% (n=29) complete responses (including one pathological complete response) and 41% (n=74) partial responses}. In evaluable patients with CNS metastases (n=22), ORR was 68% (95% CI 45-86). Among all patients, median time to response was 1.8 months and median duration of response (DoR) was 43.3 months (95% CI 29.2-not estimable [NE]) at a median follow-up of 32.3 months. Treatment-related adverse events (TRAEs) were predominantly Grade 1-2, with Grade 3-4 occurring in 14% (n=27) of patients. Responses were assessed by IRC.

Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer (Abstract 9056). In an expanded dataset (n=30) with longer follow-up, Vitrakvi demonstrated long-term efficacy and safety data in adult patients with advanced TRK fusion lung cancer, including those with CNS metastases (n=12). The results encourage wider adoption of next-generation sequencing (NGS) testing for identifying patients with solid tumors harboring NTRK gene fusions, including lung cancer. Among 27 adult patients eligible for IRC assessment with TRK fusion lung cancer enrolled, ORR was 74% (95% CI 54-89); 11% (n=3) complete responses and 63% (n=17) partial responses. Among the 12 patients with baseline CNS metastases, the ORR was 67% (95% CI 35-90), with 8 partial responses. Median DoR was 33.9 months (95% CI 9.5-NE); median follow-up was 22.9 months. TRAEs were predominantly for Grade 1-2. Grade 3-4 TRAEs were reported in 5 patients which included AST increase, ALT increase, myalgia, and hypersensitivity.

Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC) (Abstract 6091). Vitrakvi was evaluated in updated subgroup analyses of patients (n=30; data cut-off July 20, 2022) with TRK fusion thyroid cancer (TC). Among those eligible for efficacy assessment, 47% (n=14) had NTRK1 and 53% (n=16) had NTRK2. Fifty percent (n=15) of patients received no prior systemic therapies, 20% (n=6) received at least 2, and 77% (n=23) received prior radioiodine. ORR was 63% (95% CI 44-80); 10% (n=3) complete responses and 53% (n=16) partial responses. For patients classified as differentiated thyroid cancer (DTC; n=23), ORR was 78% (95% CI 56-93). For patients classified as anaplastic thyroid cancer (ATC; n=7), ORR was 14% (95% CI 0-58). All patients with CNS metastases (n=4) at baseline had a partial response. Median time to response was 1.9 months and median DoR was 43.3 months (95% CI 21.6-NE) at a median follow-up of 32.3 months. Grade at least 3 TRAEs, anemia and decreased lymphocycte count, were reported in 7% (n=2) patients. There were no treatment discontinuations due to TRAEs. Responses were assessed by IRC.