PDF herunterladen
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(03): 279-281
DOI: 10.1055/s-0041-1732823
Drug Review

Larotrectinib: A Novel Tumor-Agnostic Neurotrophic Tropomyosin Receptor Kinase (NTRK) Inhibitor in Advanced Solid Tumors

Manikandan Dhanushkodi
1   Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
,
Jyoti Bajpai
2   Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
› Institutsangaben
› Weitere Informationen
   Lizenzen und Reprints

Abstract

Larotrectinib and entrectinib are highly selective, potent tropomyosin receptor kinase fusion inhibitors. It is U.S. Food and Drug Administration approved for the treatment of adult and pediatric advanced solid tumors with neurotrophic tropomyosin receptor kinase fusion genes who are refractory to standard systemic therapy. The response rate was ~80% and was rapid and durable. The median progression-free survival was 28 months. The side effects include anemia, weight gain, hepatotoxicity, and neuropsychiatric manifestations. Phase 3, randomized controlled trials are warranted to assess survival benefit.

Keywords

larotrectinib - NTRK inhibitor - tumor agnostic therapy


Publikationsverlauf

Artikel online veröffentlicht:
18. August 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Lassen U. How I treat NTRK gene fusion-positive cancers. ESMO Open 2019; 4 (Suppl. 02) e000612
    CrossrefPubMedGoogle Scholar
  • 2 Jørgensen JT. A paradigm shift in biomarker guided oncology drug development. Ann Transl Med 2019; 7 (07) 148
    CrossrefPubMedGoogle Scholar
  • 3 Penault-Llorca F, Rudzinski ER, Sepulveda AR. Testing algorithm for identification of patients with TRK fusion cancer. J Clin Pathol 2019; 72 (07) 460-467
    CrossrefPubMedGoogle Scholar
  • 4 Marchiò C, Scaltriti M, Ladanyi M. et al ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019; 30 (09) 1417-1427
    CrossrefPubMedGoogle Scholar
  • 5 Scott LJ. Larotrectinib: first global approval. Drugs 2019; 79 (02) 201-206
    CrossrefPubMedGoogle Scholar
  • 6 Hong DS, DuBois SG, Kummar S. et al Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (04) 531-540
    CrossrefPubMedGoogle Scholar
  • 7 Drilon A, Laetsch TW, Kummar S. et al Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018; 378 (08) 731-739
    CrossrefPubMedGoogle Scholar
  • 8 Drilon A, Ou SI, Cho BC. et al Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov 2018; 8 (10) 1227-1236
    CrossrefPubMedGoogle Scholar
  • 9 Laetsch TW, DuBois SG, Mascarenhas L. et al Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 2018; 19 (05) 705-714
    CrossrefPubMedGoogle Scholar
  • 10 Hong DS, Bauer TM, Lee JJ. et al Larotrectinib in adult patients with solid tumours: a multi-centre, open-label, phase I dose-escalation study. Ann Oncol 2019; 30 (02) 325-331
    CrossrefPubMedGoogle Scholar