Abstract

BackgroundDabrafenib 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 presentationA 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.ConclusionsThis 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.

Highlights

  • Dabrafenib and trametinib combination therapy is approved for the treatment of patients with V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) V600E positive tumors including melanoma and lung cancer

  • The combination of the BRAF V600E specific inhibitor dabrafenib and the Mitogen-Activated Protein Kinase Kinase (MEK) inhibitor trametinib was approved for the treatment of BRAF V600E positive lung cancer based on a phase II study showing Progression Free Survival (PFS) of 14.6 months and response rate of 64% [10]

  • The etiology of fever is poorly understood, it is well known that the thermostat is physiologically regulated by a cytokine surge including interleukin 1α and 1β (IL1α, Interleukin 1 beta (IL1β)), interleukin 6 (IL6) and tumor necrosis factor alpha (TNFα) [13]

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Summary

Introduction

Dabrafenib and trametinib combination therapy is approved for the treatment of patients with BRAF V600E positive tumors including melanoma and lung cancer. 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. The combination of the BRAF V600E specific inhibitor dabrafenib and the MEK inhibitor trametinib was approved for the treatment of BRAF V600E positive lung cancer based on a phase II study showing PFS of 14.6 months and response rate of 64% [10].

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