Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Larkin, James; Marais, Richard; Porta, Nuria; Gonzalez de Castro, David; Parsons, Lisa; Messiou, Christina; Stamp, Gordon; Thompson, Lisa; Edmonds, Kim; Sarker, Sarah; Banerji, Jane; Lorigan, Paul; Evans, Thomas R. Jeffry; Corrie, Pippa; Marshall, Ernest; Middleton, Mark R.; Nathan, Paul; Nicholson, Steve; Ottensmeier, Christian; Plummer, Ruth; Bliss, Judith; Valpione, Sara; Turajlic, Samra

doi:10.1016/j.xcrm.2024.101435

Cited by 4 publications

References 65 publications

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Real-world evidence on efficacy and toxicity of targeted therapy in older melanoma patients treated in a tertiary-hospital setting

Stoff,

Markovic,

McWilliams

et al. 2024

Melanoma Research

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Melanoma is the deadliest form of skin cancer. The median age at diagnosis is 66. While most patients are treated with immunotherapy, the use of targeted therapy is a valid alternative for patients whose tumors harbor a BRAF or c-KIT driver mutation. These agents, while effective, come with a variety of side effects which limit their use, especially in older patients. We sought to assess the efficacy and toxicity of these agents in older melanoma patients. Melanoma patients over 65 treated with BRAF/MEK or c-KIT inhibitors were retrospectively identified, and their data were analyzed for treatment efficacy and toxicity. All data were compared using the Chi-square test for categorical comparisons and the Kruskal–Wallis method for median comparisons. One hundred and sixteen patients were identified. One hundred and six patients were treated with BRAF/MEK inhibitors. The assessed response rate (RR) was 83% and was comparable across different subgroups, including advanced line patients and those with a more aggressive disease. The median progression free survival (PFS) was 7.9 months, and the median overall survival (OS) was 15.7 months. Twenty-seven percent experienced grade 3–4 toxicity leading to a 24% treatment discontinuation rate. Another 10 patients were treated with the c-KIT inhibitor imatinib, for whom the assessed RR was 55%. The median PFS was 4.3 months, and the median OS was 22.6 months. Forty percent needed dose reductions, yet none had to stop treatment due to adverse effects. The use of targeted therapy in older patients is effective yet challenging due to toxicity. Deploying mitigation strategies can help maximizing their usefulness.

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Real-world evidence on efficacy and toxicity of targeted therapy in older melanoma patients treated in a tertiary-hospital setting

Stoff,

Markovic,

McWilliams

et al. 2024

Melanoma Research

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Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy

Blacklock,

Donnelly,

et al. 2024

Preprint

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Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for pre-clinical trials. Comprehensive data on this tumour type is scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary oronasal mucosal melanoma (OMM) cohort of treatment naive archival tissue, alongside clinicopathological data, we obtained transcriptomic immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species, and linked our findings to immunohistochemical, microbiome and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups which we defined using a species-independent 41-gene signature. These two subgroups are termed CTLA4- high and cMET-high, and indicate actionable targets for OMM patients. To guide clinical decision-making, we developed immunohistochemical diagnostic tools which distinguish between transcriptomic subgroups. For the first time, we find that OMM has conserved transcriptomic subtypes and biological similarity between the canine and human OMM, with significant implications for patient classification, treatment, and clinical trial design.

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Curing Stage IV Melanoma: Where Have We Been and Where Are We?

Chan,

Corrie

2024

Am Soc Clin Oncol Educ Book

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Little more than 10 years ago, metastatic melanoma was considered to have one of the poorest cancer outcomes, associated with a median overall survival of 6-8 months. Cytotoxic chemotherapy offered modest response rates of 20%-30%, but no clear survival benefit. Patients were routinely enrolled in clinical trials as their first-line therapy in the search for effective novel therapeutics. Remarkable developments in molecular biology, cancer genomics, immunology, and drug discovery have dominated the early part of the 21st century, and nowhere have the benefits been better realized than in the transformation of outcomes for patients with metastatic melanoma: since 2011, 14 new agents have been approved that significantly increase survival, with long-term remissions and, possibly now, potential for cure. Even so, there is still much work to be done, given that most treated patients still die of their disease. Although most survival gains have so far been realized for cutaneous melanoma, improving treatment options for those 10% of patients with rarer, noncutaneous melanomas is a high priority. Key novel therapeutic approaches aimed at improving outcomes with potential for curing patients with melanoma are considered.

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Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Cited by 4 publications

References 65 publications

Real-world evidence on efficacy and toxicity of targeted therapy in older melanoma patients treated in a tertiary-hospital setting

Real-world evidence on efficacy and toxicity of targeted therapy in older melanoma patients treated in a tertiary-hospital setting

Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy

Curing Stage IV Melanoma: Where Have We Been and Where Are We?

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