Mixed response and mechanisms of resistance to larotrectinib in metastatic carcinoma ex pleomorphic adenoma of the parotid harboring an NTRK2 fusion: A case report.
Adenoma, Pleomorphic
/ drug therapy
Drug Resistance, Neoplasm
Humans
Male
Membrane Glycoproteins
Middle Aged
Neoplasm Recurrence, Local
Oncogene Proteins, Fusion
/ genetics
Parotid Neoplasms
/ drug therapy
Pharyngeal Neoplasms
/ drug therapy
Protein Kinase Inhibitors
/ therapeutic use
Pyrazoles
/ therapeutic use
Pyrimidines
/ therapeutic use
Receptor, trkB
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
29 Jan 2021
29 Jan 2021
Historique:
received:
29
10
2020
accepted:
06
01
2021
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
13
2
2021
Statut:
ppublish
Résumé
Standardized systemic treatment options are lacking for carcinoma ex pleomorphic adenoma, which is a rare and aggressive tumor primarily found in salivary glands.Here we report the case of a 63-year-old male with carcinoma ex pleomorphic adenoma of the left parotid and parapharyngeal space harboring a neurotrophic receptor tyrosine kinase (NTRK) 2 fusion who was treated with a small molecule inhibitor that targets the tropomyosin receptor kinase (TRK) proteins. To the best of our knowledge, no similar case has been described in the literature so far. After multiple surgical resections and radiotherapy for localized cancer disease over several years, our patient again developed an increasing swelling and pain around the left ear and numbness of the left half of the face. Magnetic resonance imaging and positron emission tomography/computed tomography scans showed tumor recurrence in the left parotid, below the left ear, and in the parapharyngeal space, as well as metastases of the lungs and cervical lymph nodes. As data on the efficacy of systemic therapies for inoperable carcinoma ex pleomorphic adenoma are scarce, we performed a next-generation sequencing that revealed the presence of a hitherto unknown NTRK2 fusion. Treatment with the TRK inhibitor larotrectinib was initiated, which induced rapid symptom improvement. However, part of the tumor had to be removed shortly afterwards due to local progression. Molecular testing did not demonstrate any alterations accounting for resistance to larotrectinib, with maintenance of the NTRK2 fusion. Three months later, imaging confirmed mixed response. While the reason for this remains unknown, the patient is in good condition and continues to receive larotrectinib. It remains unclear why our patient showed mixed response to larotrectinib and further studies are needed to explore other possible mechanisms of resistance.
Identifiants
pubmed: 33530256
doi: 10.1097/MD.0000000000024463
pii: 00005792-202101290-00106
pmc: PMC7850688
doi:
Substances chimiques
Membrane Glycoproteins
0
Oncogene Proteins, Fusion
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Pyrimidines
0
Receptor, trkB
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
larotrectinib
PF9462I9HX
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e24463Informations de copyright
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors have no conflicts of interests to disclose.
Références
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