Rapid Readouts: Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase (TRK) Fusion-Positive Lung Cancer

OncLive® Rapid Readout from World Cancer Lung Conference 2021: Results for Larotrectinib in Patients With TRK Fusion-Positive Lung Cancer

Segment Description:

Alexander Drilon, MD, discusses data from the following presentation: “Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase (TRK) Fusion-Positive Lung Cancer.” (IASLC Drilon Abstract P53.02)

Segment Body Content:

• Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in a range of tumor types. Larotrectinib, a central nervous system (CNS)-active and highly selective EMA- and FDA-approved TRK inhibitor, demonstrated an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 months across multiple cancers (Hong et al. Lancet Oncol 2020).
• Methods
  • Patients with lung cancer harboring an NTRK gene fusion enrolled in 2 clinical trials were pooled for this analysis.
  • Larotrectinib 100 mg BID was administered on a continuous 28-day schedule. Response was assessed by the investigator per RECIST v1.1.
• Results
  • 14 patients with metastatic TRK fusion lung cancer were enrolled—13 with non-small cell lung cancer and 1 with small cell lung cancer.
  • Median age: 52 years (range 25-76)
  • Eleven patients had fusions involving NTRK1, and 3 patients had fusions involving NTRK3.
  • Seven patients had baseline CNS metastases.
  • Patients were heavily pre-treated with a median of 3 prior therapies (range 1-5).
    • Nine patients had received 2 prior therapies.
  • ORR with Larotrectinib: 71% (95% CI 42-92%).
    • One patient had a complete response, 9 had partial responses, 3 had stable disease, and 1 had progressive disease.
  • ORR with CNS metastases: 57% (95% CI 18-90).
  • Overall DoR ranged from 1.9+ to 28.7+ months.
  • Median progression-free survival (PFS) had not been reached (range 1.8-30.3+ months), with an estimated PFS rate at 12 months of 69%.
  • Treatment duration ranged from 2.1 to 39.6+ months. Larotrectinib was well tolerated, with treatment-emergent adverse events being mainly grade 1-2.
• Conclusions
  • Larotrectinib was shown to be highly active in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. The drug has a favorable safety profile. These results support inclusion of NTRK gene fusions in routine molecular testing of patients with lung cancer.