Real-world experience of tropomyosin receptor kinase inhibition with entrectinib in ETV6-NTRK3 positive metastatic salivary secretory carcinoma: A case series

Head Neck. 2023 May;45(5):E10-E15. doi: 10.1002/hed.27346. Epub 2023 Mar 16.

Abstract

Background: The efficacy of entrectinib, a potent inhibitor of tropomyosin receptor kinases, c-ros oncogene 1, and anaplastic lymphoma kinase has been demonstrated in neurotrophic receptor tyrosine kinase fusion-positive pediatric and adult solid tumors. However, real-world data on entrectinib therapy for salivary gland malignancies are limited.

Methods: We describe a multicenter case series of four consecutive patients with ETV6-NTRK3 fusion-positive metastatic salivary secretory carcinoma (SSC) treated with entrectinib.

Results: All patients had a prior history of systemic therapy with cytotoxic chemotherapy or immune checkpoint inhibitors. All patients achieved durable radiographic complete response. Adverse events included weight gain, dizziness, increase in creatine kinase level, and withdrawal pain, but were manageable by the interruption and dose reduction of entrectinib.

Conclusion: Durable complete response was achieved with entrectinib in patients with ETV6-NTRK3 fusion-positive metastatic SSC. The clinical benefit of entrectinib supports the importance of routine screening for NTRK gene fusion in patients with SSC.

Trial registration: ClinicalTrials.gov NCT02568267.

Keywords: ETV6-NTRK3; complete response; entrectinib; molecular screening; salivary secretory carcinoma.

Publication types

  • Multicenter Study
  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma* / pathology
  • Child
  • Humans
  • Oncogene Proteins, Fusion / genetics
  • Tropomyosin*

Substances

  • entrectinib
  • Tropomyosin
  • Oncogene Proteins, Fusion
  • ETV6-NTRK3 fusion protein, human

Supplementary concepts

  • Secretory breast carcinoma

Associated data

  • ClinicalTrials.gov/NCT02568267