Tropomyosin receptor kinase inhibitors in the management of sarcomas.
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Embargo End Date
ICR Authors
Authors
Wilding, CP
Loong, HH
Huang, PH
Jones, RL
Loong, HH
Huang, PH
Jones, RL
Document Type
Journal Article
Date
2020-06-05
Date Accepted
Abstract
PURPOSE OF REVIEW: Genetic aberrations resulting in tropomyosin receptor kinase (TRK) fusion proteins can drive oncogenesis and are postulated to occur in up to 1% of solid tumours. However, TRK fusions in adult sarcomas are rare and there is a significant challenge in identifying patients with sarcomas harbouring TRK fusions in the clinical setting. Despite a recent European Society of Medical Oncology consensus article regarding screening of tumours for TRK fusions, economical and practical limitations present a barrier to widespread screening of sarcomas. RECENT FINDINGS: Larotrectinib and entrectinib are pan-TRK inhibitors which have both received FDA approval for the management of solid tumours harbouring NTRK fusions. Initial results of a number of clinical trials have demonstrated promising efficacy and safety data, including dramatic and durable responses in patients with sarcomas. As such, TRK inhibitors represent a promising treatment option in a small cohort of adult sarcoma patients, where currently treatment options are limited. The emergence of acquired resistance is a concern associated with TRK inhibitor therapy and a number of second-generation agents targeting TRK kinase mutations driving acquired resistance have entered early-phase clinical trials. SUMMARY: With the growing appreciation of the implications of TRK fusions, this review will summarize the emerging clinical trial data of TRK inhibitors in sarcomas. Although in their infancy, clinical trial results are encouraging, and as further results and analyses are released, we will have a greater understanding of their impact on clinical practice and the management of patients with sarcomas.
Citation
Current opinion in oncology, 2020, 32 (4), pp. 307 - 313
Source Title
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
1040-8746
eISSN
1531-703X
Collections
Research Team
Molecular and Systems Oncology