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133 Dramatic responses to Dabrafenib – challenges for palliative care providers in the new era of targeted therapy and immunotherapy
  1. Mairéad Doherty and
  2. Sarah McLean
  1. Our Lady’s Hospice and Care Services, St Vincent’s Private Hospital, Dublin


Background Immunotherapy has improved the survival associated with many cancers, changing the landscape of oncological management. This paradigm shift confronts palliative care providers with novel clinical dilemmas. We describe two cases in which a dramatic response to immunotherapy led to a rapid improvement in symptoms, requiring prompt clinical management.

Case 1 A 32 year-old woman with extensively metastatic malignant melanoma presented with worsening headache and abdominal pain. Imaging demonstrated progression of disease on pembrolizumab.

Management - BRAF mutation analysis confirmed V600 mutation. Upon commencement of dabrafenib 150 mg twice daily analgesia included hydromorphone 12 mg/24 hours subcutaneously, pregabalin 50 mg three times daily, dexamethasone 8 mgs twice daily, regular diclofenac and paracetamol.

Outcome - Within 48 hours, the patient developed opioid toxicity with respiratory depression. Hydromorphone was held, and restarted at 6mg/24hours. Within 7 days the dose was reduced to 3mg/24hours due to adequate pain control. Imaging confirmed disease response. After a period of rehabilitation the patient was discharged on palladone SR 2 mg twice daily.

Case 2 A 56 year-old woman with a 5-year history of non-small cell lung cancer (confirmed BRAF-mutated) presented in acute liver failure, with almost complete tumour replacement of the liver parenchyma.

Management - At presentation, she was on a treatment break from dabrafenib, due to intolerable nausea. On re-challenge, nausea recurred. However, with aggressive anti-emetic management, including ondansetron 24mgs/24 hours subcutaneously, she tolerated an initial dose of dabrafenib 50 mgs daily, and subsequently 150 mgs.

Outcome - Her liver function began to improve within 24 hours of commencing dabrafenib. Within 8 days, she demonstrated signs of opioid toxicity, and became severely constipated, requiring discontinuation of subcutaneous fentanyl and ondansetron. She was discharged home 2 weeks later with essentially normal liver function.

Conclusion Immunotherapy continues to revolutionise oncological management, and as this treatment modality evolves, is likely to present further challenges for palliative care providers.

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