MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient.
Humans
Pyridones
/ administration & dosage
Pyrimidinones
/ administration & dosage
Male
Oximes
/ administration & dosage
Aged
Proto-Oncogene Proteins B-raf
/ genetics
Imidazoles
/ administration & dosage
Lung Neoplasms
/ drug therapy
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Drug Resistance, Neoplasm
Proto-Oncogene Proteins c-met
/ genetics
Mutation
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
medline:
8
8
2024
pubmed:
8
8
2024
entrez:
8
8
2024
Statut:
ppublish
Résumé
The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance.
Identifiants
pubmed: 39115059
doi: 10.1097/CAD.0000000000001623
pii: 00001813-202409000-00009
doi:
Substances chimiques
Pyridones
0
dabrafenib
QGP4HA4G1B
trametinib
33E86K87QN
Pyrimidinones
0
Oximes
0
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Imidazoles
0
Proto-Oncogene Proteins c-met
EC 2.7.10.1
BRAF protein, human
EC 2.7.11.1
MET protein, human
EC 2.7.10.1
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
761-763Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
Leonetti A, Facchinetti F, Rossi G, Minari R, Conti A, Friboulet L, et al. BRAF in non-small cell lung cancer (NSCLC): pickaxing another brick in the wall. Cancer Treat Rev 2018; 66:82–94.
Planchard D, Besse B, Groen HJM, Souquet P-J, Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 2016; 17:984–993.
Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland A, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol 2017; 18:1307–1316.
Tsamis I, Gomatou G, Chachali SP, Trontzas IP, Patriarcheas V, Panagiotou E, et al. BRAF/MEK inhibition in NSCLC: mechanisms of resistance and how to overcome it. Clin Transl Oncol 2023; 25:10–20.
Chou YT, Lin CC, Lee CT, Pavlick DC, Su PL. Durable response of dabrafenib, trametinib, and capmatinib in an NSCLC patient with co-existing BRAF-KIAA1549 fusion and MET amplification: a case report. Front Oncol 2022; 12:838798.