Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipi + nivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.
Combination therapy with dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to dabrafenib or vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less common but side effects such as fever and nausea more common. How dabrafenib/trametinib is best sequenced with other effective treatments such as immune checkpoint blockade remains uncertain.
Introduction: Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin-dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered: This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen.
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