Larotrectinib followed by selitrectinib in a novel DCTN1-NTRK1 fusion undifferentiated pleomorphic sarcoma

INTRODUCTION: Neurotrophic receptor tyrosine kinase fusions cause overexpression or activation of kinase and are believed to confer oncogenic potential in some non-rhabdomyosarcoma soft tissue sarcomas. TRK inhibitors have recently been shown to induce responses in these tumours though current experience with these agents is still limited.

CASE REPORT: We report a case of an adolescent with treatment-refractory non-rhabdomyosarcoma soft tissue sarcomas, carrying a novel DCTN1-NTRK1 gene fusion whose progressive disease was treated with multi-kinase and TRK inhibitors.Management and outcome: Our patient was started on pan-TRK inhibitor larotrectinib, as his disease progressed after chemotherapy, radiation therapy and surgery, based on next-generation sequencing test showing DCTN1-NTRK1 gene fusion. He responded quickly to larotrectinib with the improvement of symptoms and reduction of masses. However, this response was short-lived due to the development of acquired solvent front resistance mutation. This patient did not respond to next-generation TRK inhibitor selitrectinib and eventually succumbed to his disease.

DISCUSSION: The initial rapid and drastic response of our patient to larotrectinib was not sustained due to the development of acquired resistance. This case emphasizes the need for upfront and periodic next-generation sequencing testing to guide treatment of patients with refractory non-rhabdomyosarcoma soft tissue sarcomas.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners - 27(2021), 2 vom: 02. März, Seite 485-489

Sprache:

Englisch

Beteiligte Personen:

Goh, Xue Na [VerfasserIn]
Seng, Michaela Su-Fern [VerfasserIn]
Loh, Amos Hong Pheng [VerfasserIn]
Gupta, Achint [VerfasserIn]
Chang, Kenneth Tou En [VerfasserIn]
Iyer, Prasad [VerfasserIn]

Links:

Volltext

Themen:

0J45910S3X
Antineoplastic Agents
Aza Compounds
Case Reports
DCTN1 protein, human
Dynactin Complex
EC 2.7.10.1
Journal Article
Larotrectinib
NTRK1 protein, human
Neurotrophic receptor tyrosine kinase fusions
Non-rhabdomyosarcoma soft tissue sarcomas
Oncogene Proteins, Fusion
PF9462I9HX
Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Receptor, trkA
Selitrectinib
TRK inhibitor resistance

Anmerkungen:

Date Completed 29.03.2021

Date Revised 07.04.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/1078155220938849

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312699050