Rapid Readouts: Results from two trials of TRK inhibitor, larotrectinib, in patients with TRK fusion-positive lung cancer

Alexander Drilon, MD, discusses data from the following presentation:

• Long-term efficacy and safety of larotrectinib in patients with TRK fusion-positive lung cancer (Lin, 2021 ASCO Annual Meeting, abstract # 9109)
  • The objective of this presentation is to report updated results in patients with TRK fusion-positive lung cancers from the phase II adult/pediatric NAVIGATE basket trial (NCT02576431) and an adult phase 1 trial (NCT02122913) where patients were treated with larotrectinib.
  • Baseline characteristics
    • Central nervous system (CNS) metastases at baseline: 10 (50%) yes, 10 (50%) no
    • NTRK gene fusions (n = 20): NTRK1 80%; NTRK2 0%; NTRK3 20%
    • Tumor histology: 19 (95%) adenocarcinoma, 1 (5%) neuroendocrine carcinoma
  • Conclusions: efficacy
    • In all evaluable patients (n = 15), the overall response rate (ORR) was 73%, including 1 (7%) complete response, 10 (67%) partial response, 3 (20%) stable disease, and 1 (7%) progressive disease; responses were durable with a median progression-free survival (PFS) of 35.4 months and median duration of response of 33.9 months. Median overall survival was 40.7 months.
    • In patients with CNS metastases (n = 10), the ORR was 63%, including 5 (52%) partial response, 2 (25%) stable disease, and 1 (13%) progressive disease.
  • Conclusions: safety
    • Treatment-related adverse events (TRAEs) were predominantly grade 1 and 2.
    • TRAEs were reported by 16 patients (80%); 2 patients (10%) experienced grade 3 TRAE (myalgia, hypersensitivity, and weight increase).
    • Two patients (10%) required dose reduction due to AEs: grade 2 ALT and grade 2 AST increase in 1 patient and grade 2 neutrophil count decrease in the other patient; there were no treatment discontinuations due to AEs.