Granulomatosis with polyangiitis in a patient treated with dabrafenib and trametinib for BRAF V600E positive lung adenocarcinoma.


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
04 Mar 2020
Historique:
received: 12 10 2018
accepted: 20 02 2020
entrez: 6 3 2020
pubmed: 7 3 2020
medline: 24 10 2020
Statut: epublish

Résumé

Dabrafenib and trametinib combination therapy is approved for the treatment of patients with BRAF V600E positive tumors including melanoma and lung cancer. The effect of BRAF and MEK inhibitors on the immune system is not fully understood although a number of case reports indicate autoimmune side effects related to the use of these drugs. Here, we discuss a case of a patient diagnosed with granulomatosis with polyangiitis (GPA) shortly after starting treatment with dabrafenib and trametinib for BRAF V600E positive metastatic lung adenocarcinoma. A 57 years old female patient was diagnosed with recurrent lung adenocarcinoma following initial lobectomy for early stage disease. A BRAF V600E mutation was identified at the time of recurrence and she received combination dabrafenib and trametinib therapy. Shortly after commencement of treatment, she developed persistent fevers necessitating withholding both drugs. Pyrexia continued and was followed by left vision loss and acute kidney injury. Further rheumatological workup led to the unifying diagnosis of GPA. The patient was then treated with rituximab for GPA to the present date while all antineoplastic drugs were held. Lung cancer oligoprogression was addressed with radiation therapy and has not required further systemic treatment whereas GPA has been controlled to-date with rituximab. This case report raises awareness among clinicians treating patients with lung cancer for the possibility of triggering a flare of autoimmune diseases like GPA in patients with BRAF V600E positive lung cancer receiving treatment with BRAF directed therapy.

Sections du résumé

BACKGROUND BACKGROUND
Dabrafenib and trametinib combination therapy is approved for the treatment of patients with BRAF V600E positive tumors including melanoma and lung cancer. The effect of BRAF and MEK inhibitors on the immune system is not fully understood although a number of case reports indicate autoimmune side effects related to the use of these drugs. Here, we discuss a case of a patient diagnosed with granulomatosis with polyangiitis (GPA) shortly after starting treatment with dabrafenib and trametinib for BRAF V600E positive metastatic lung adenocarcinoma.
CASE PRESENTATION METHODS
A 57 years old female patient was diagnosed with recurrent lung adenocarcinoma following initial lobectomy for early stage disease. A BRAF V600E mutation was identified at the time of recurrence and she received combination dabrafenib and trametinib therapy. Shortly after commencement of treatment, she developed persistent fevers necessitating withholding both drugs. Pyrexia continued and was followed by left vision loss and acute kidney injury. Further rheumatological workup led to the unifying diagnosis of GPA. The patient was then treated with rituximab for GPA to the present date while all antineoplastic drugs were held. Lung cancer oligoprogression was addressed with radiation therapy and has not required further systemic treatment whereas GPA has been controlled to-date with rituximab.
CONCLUSIONS CONCLUSIONS
This case report raises awareness among clinicians treating patients with lung cancer for the possibility of triggering a flare of autoimmune diseases like GPA in patients with BRAF V600E positive lung cancer receiving treatment with BRAF directed therapy.

Identifiants

pubmed: 32131760
doi: 10.1186/s12885-020-6661-6
pii: 10.1186/s12885-020-6661-6
pmc: PMC7057580
doi:

Substances chimiques

Imidazoles 0
Oximes 0
Pyridones 0
Pyrimidinones 0
trametinib 33E86K87QN
Rituximab 4F4X42SYQ6
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1
dabrafenib QGP4HA4G1B

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

177

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Auteurs

Anastasios Dimou (A)

Division of Medical Oncology, University of Colorado, Anschutz Medical Campus, 13001 E 17th Pl, Aurora, CO, 80045, USA. Anastasios.dimou@ucdenver.edu.

Gregory Barron (G)

Division of Rheumatology, University of Colorado, Anschutz Medical Campus, 13001 E 17th Pl, Aurora, CO, 80045, USA.

Daniel T Merrick (DT)

Department of Pathology, University of Colorado, School of Medicine, 13001 E 17th Pl, Aurora, CO, 80045, USA.

Jason Kolfenbach (J)

Division of Rheumatology, University of Colorado, Anschutz Medical Campus, 13001 E 17th Pl, Aurora, CO, 80045, USA.

Robert C Doebele (RC)

Thoracic Oncology Research Initiative, Division of Medical Oncology, University of Colorado, School of Medicine, 12801 E. 17th Ave., MS 8117, Aurora, CO, 80045, USA.

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Classifications MeSH