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


Alexander Drilon, MD, discusses the efficacy and safety data of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion-positive lung cancer that was presented at the World Cancer Lung Conference 2021 annual meeting.

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.
Related Videos
Joshua K. Sabari, MD, an expert on lung cancer, presenting slides
Chul Kim, MD, MPH
Salman R. Punekar, MD, Mayo Clinic
Federico Cappuzzo, MD