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Dabrafenib/trametinib/vemurafenib Emergence of drug resistance, adverse effect on the skin and lack of efficacy: case report

A 29-year-old woman developed adverse effect on the skin and had emergence of drug resistance during treatment with vemurafenib for epithelioid glioblastoma (Ep-GBM). Additionally, she exhibited lack of efficacy during treatment with dabrafenib and trametinib for Ep-GBM [routes, exact duration of treatment to reaction onset and outcomes not stated]. The woman suffered from seizures with a headache. She had undergone craniotomy due to the development of mass lesions in the left temporal and occipital lobes. Based on further pathological examination, a diagnosis of Ep-GBM was made. Ten days after craniotomy, she had lower limb pain and a head MRI demonstrated cerebral ventricular dissemination. Subsequently, she received Ommaya capsule implantation. Thereafter, in 2017, she was admitted to the current hospital and started on temozolomide, methotrexate and cytarabine regimen. Despite treatment, the lower limb pain and headache worsened with tumour progression. Subsequently, she underwent radiotherapy and no improvement in the disease state, lower limb pain and headache were noted. The gene test revealed the existing BRAFV600E mutation. Therefore, she was started on vemurafenib 480mg twice daily. Five days later, the lower limb pain and headache resolved with tumour relief. However, she developed a grade 2 adverse effect on the skin. The woman’s vemurafenib treatment was discontinued. Meanwhile, her symptoms worsened and progression in the tumour was noted. Therefore, she was re-started on vemurafenib at 960mg twice daily. However, she developed a grade 3 adverse effect on the skin, which led to discontinuation of vemurafenib treatment. Subsequently, progression in tumour size was observed, which suggested the development of resistance to the vemurafenib treatment. She then initiated on dabrafenib 150mg twice daily and trametinib 2mg daily with no effect. Finally, after a overall survival of 12 months she died [immediate cause of death not stated]. Li Y, et al. Effect of BRAF/MEK inhibition on epithelioid glioblastoma with BRAFV600E mutation: A case report and review of the literature. Clinical Laboratory: Journal for Clinical Laboratories and Laboratories Related to Blood Transfusion 66: 1629-1633, No. 8, Jan 2020. Available from: URL: http://doi.org/10.7754/ Clin.Lab.2020.191134 803503977

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Reactions 26 Sep 2020 No. 1823