Granulomatosis with polyangiitis in a patient treated with dabrafenib and trametinib for BRAF V600E positive lung adenocarcinoma.
Adenocarcinoma of Lung
/ drug therapy
Amino Acid Substitution
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Female
Granulomatosis with Polyangiitis
/ chemically induced
Humans
Imidazoles
/ administration & dosage
Lung Neoplasms
/ drug therapy
Middle Aged
Oximes
/ administration & dosage
Proto-Oncogene Proteins B-raf
/ genetics
Pyridones
/ administration & dosage
Pyrimidinones
/ administration & dosage
Rituximab
/ therapeutic use
Treatment Outcome
Autoimmune side effects
MAPK
MEK inhibitor
P-ANCA
Pyrexia
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
04 Mar 2020
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
177Références
Blood. 2001 Oct 1;98(7):2175-82
pubmed: 11568005
Rheumatology (Oxford). 2018 Aug 1;57(8):1497-1499
pubmed: 29617934
J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1797-806
pubmed: 25752368
Eur J Dermatol. 2015 Apr;25(2):177-80
pubmed: 25788221
Sci Transl Med. 2015 Mar 18;7(279):279ra41
pubmed: 25787767
Ther Adv Med Oncol. 2015 Mar;7(2):122-36
pubmed: 25755684
Nat Rev Rheumatol. 2019 Feb;15(2):91-101
pubmed: 30542206
Cancer Res. 2010 Jul 1;70(13):5213-9
pubmed: 20551059
Am J Dermatopathol. 2014 Jun;36(6):493-7
pubmed: 24879511
Sci Rep. 2017 Jul 5;7(1):4666
pubmed: 28680105
Infect Immun. 2002 May;70(5):2519-25
pubmed: 11953391
Cancer Immunol Res. 2014 Apr;2(4):351-60
pubmed: 24764582
Lancet Oncol. 2017 Oct;18(10):1307-1316
pubmed: 28919011
Nat Rev Cancer. 2017 Nov;17(11):676-691
pubmed: 28984291
Ann Oncol. 2017 Nov 1;28(11):2648-2657
pubmed: 29045527
Clin Cancer Res. 2015 Apr 1;21(7):1639-51
pubmed: 25589619
Clin Nucl Med. 2017 Jan;42(1):44-46
pubmed: 27775948
J Infect Dis. 1999 Mar;179 Suppl 2:S294-304
pubmed: 10081499
BMC Cancer. 2015 Oct 19;15:732
pubmed: 26481107
Immunity. 2016 Mar 15;44(3):609-621
pubmed: 26944201
Am J Surg Pathol. 1991 Apr;15(4):315-33
pubmed: 2006712
J Immunol. 2009 Dec 15;183(12):8258-67
pubmed: 20007589
Am J Surg Pathol. 1990 Jun;14(6):555-64
pubmed: 2337204
N Engl J Med. 2017 Nov 9;377(19):1813-1823
pubmed: 28891408
Mol Cancer Ther. 2011 Mar;10(3):385-94
pubmed: 21388974
Nature. 2002 Jun 27;417(6892):949-54
pubmed: 12068308
Methods Mol Biol. 2010;661:471-80
pubmed: 20812002
Blood. 2012 Jan 5;119(1):188-91
pubmed: 22072557
J Thorac Oncol. 2016 Dec;11(12):2129-2140
pubmed: 27615396
Infection. 1992;20 Suppl 2:S124-7
pubmed: 1493936
J Clin Oncol. 2011 May 20;29(15):2046-51
pubmed: 21483012
Nat Rev Immunol. 2015 Jun;15(6):335-49
pubmed: 25976513
J Clin Oncol. 2007 Apr 20;25(12):1606-20
pubmed: 17443002
Autoimmunity. 2010 Feb;43(1):17-22
pubmed: 19961364