Activity of larotrectinib in TRK fusion cancer patients with primary central nervous system tumours

Date 23 November 2019
Event ESMO Asia Congress 2019
Session Poster display session
Topics Central Nervous System Malignancies
Personalised/Precision Medicine
Presenter David Ziegler
Citation Annals of Oncology (2019) 30 (suppl_9): ix122-ix130. 10.1093/annonc/mdz431
Authors D.S. Ziegler1, F. Doz2, B. Geoerger3, S. Dubois4, J.E. Grilley-Olson5, C. van Tilburg6, A. Italiano7, A. Lissat8, J. Kang9, M. Tahara10, V. Boni11, S. Perreault12, M. Capra13, S. Nanda14, N. Brega15, A. Holynskyj16, D.S. Hong17, D. Hyman18, A. Drilon19
  • 1Kids Cancer Centre, Sydney Children’s Hospital, 2031 - Randwick/AU
  • 2Institut Curie, Siredo Oncology Center (care, Innovation And Research For Children And Aya With Cancer), Paris Descartes University, Paris/FR
  • 3Gustave Roussy Cancer Center, Université Paris-Sud, Université Paris-Saclay, Villejuif/FR
  • 4Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston/US
  • 5Lineberger Cancer Center, University of North Carolina Hospitals, Chapel Hill/US
  • 6Hopp Children’s Cancer Center Heidelberg (kitz), Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg/DE
  • 7Department Of Medical Oncology, Institute Bergonie, Bordeaux/FR
  • 8Virchow-klinikum Medizinische Klinik Mit Schwerpunkt Kardiologie, Universitätsmedizin Berlin Charite Campus, Berlin/DE
  • 9Department Of Medical Oncology, Seoul St Marys Hospital, Seoul/KR
  • 10Head And Neck Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 11Start Madrid, START Madrid CIOCC, Madrid/ES
  • 12Department Of Neurology, CHU Sainte Justine, Montreal/CA
  • 13Department Of Radiology, Our Lady Children's Hospital, Dublin/IE
  • 14Biostatistics, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 15Oncology Clinical Department, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 16Bayer, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 17Department Of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston/US
  • 18Department Of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York/US
  • 19Thoracic Oncology Service, Division Of Solid Tumor Oncology, Department Of Medicine, Memorial Sloan Kettering Cancer Center, New York/US

Abstract

Background

TRK fusions are oncogenic drivers of a variety of tumors, many of which can involve the central nervous system (CNS). Larotrectinib is an FDA-approved selective TRK inhibitor for the treatment of TRK fusion cancer (Drilon et al., NEJM 2018). Here we report on the clinical activity of larotrectinib in an expanded set of TRK fusion-positive primary CNS tumors.

Methods

Patients with primary CNS tumors harboring an NTRK gene fusion detected by local molecular testing who were treated with larotrectinib in two clinical trials (NCT02637687 and NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was investigator assessed (RANO). Data cutoff: February 19, 2019.

Results

18 patients with various histological types of glial tumors (11 high grade, 4 low grade, 3 unknown) were identified. The patients had gene fusions involving NTRK2 (n = 13), NTRK1 (n = 3) and NTRK3 (n = 2). Median age was 10.5 years (range 1.3–79.0); 14 patients were pediatric (< 18). In 14 evaluable patients, the objective response rate was 36% (2 CR [pending confirmation], 3 PR), with responses seen in high- and low-grade disease and across histologies. Nine patients had SD. The 24-week disease control rate was 71%. The duration of treatment ranged from 0.03+ to 16.6+ months.

Conclusions

Larotrectinib is active in patients with TRK fusion cancer with intracranial disease. Objective responses and durable disease control were seen in primary CNS tumors of various grades and histologies. These results further support expanded testing for NTRK gene fusions in patients with primary CNS tumors.

Clinical trial identification

NCT02637687 and NCT02576431.

Editorial acknowledgement

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

All authors have declared no conflicts of interest.