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Forward momentum in melanoma

The Gathering Around Cancer 2021 conference heard from Dr Derek Power, Consultant Medical Oncologist, Cork University Hospital (CUH), who provided an ‘Update on systemic therapy in melanoma’. Dr Power described how this treatment has “changed dramatically over the past decade… now we have so many drugs, when for many years there was nothing that was definitively proven to confer a survival advantage.

Now, we have many drugs in a variety of different settings that have been shown to confer a major benefit. The algorithm, which was distinctly bland 15 or 20 years ago, is now very busy, analogous to other solid tumour cancers.” Melanoma tumours have been sequenced and the BRAF gene identified, among others, which has led in large part to these dramatic changes, said Dr Power. BRAF mutation has led to discovery of drugs that target this pathway, with “remarkably consistent results across trials”, Dr Power added.

He provided an overview of trial data on targeted therapies, as well as other BRAF and MEK inhibitor drugs and told the attendees: “As we know, cancers are chaos and there is significant mutational burden, and this appears to correlate with efficacy for checkpoint inhibitors – it’s no surprise that melanoma is top of the list due to its aetiology of damage to DNA from skin.” He also delivered a brief overview of drug development in melanoma and said there is now increased interest in the combination of immune checkpoint inhibition and targeted therapies.

He also discussed adjuvant therapies and told the conference: “Really, we have gone from nothing with interferon, to ipilimumab in 2016, and since 2017, with anti-PD1 immunotherapy such as nivolumab and pembrolizumab, and targeted therapies such as vemurafenib and dabrafenib + trametinib, with promising survival rates with selected combinations.

We have come a long way in melanoma and in my opinion, a really interesting area is the neoadjuvant setting,” said Dr Power. “This is interesting in melanoma because significant amounts of patients in the adjuvant studies, particularly those with macro-metastases, progressed before being enrolled in the adjuvant studies, so this is a real area of interest.”

He continued: “The evidence for this is accumulating. Survival is poor with adjuvant therapy, surgery can be morbid
when resecting stage 3 disease, there are no curative biomarkers to guide prognosis, and we need to better understand why patients develop resistance,” he said.

“There is a precedence for this strategy in other solid tumour cancers. The neoadjuvant landscape is becoming very busy and there are many trials that have been published, albeit with small populations, but with very provocative pathological complete response rates from giving run-ins of dabrafenib + trametinib, run-ins of nivolumab + ipilimumab, and we really need combination immunotherapy run-ins in the neoadjuvant trials to get significant results.”

Whilst this does not represent level 1 evidence and is hypothesis-generating, the trials show very early promise, he added. During an interactive Q&A session, Dr Power commented on the need for patient education in terms of treatment strategies. “That’s absolutely critical,” he told the conference. “Education of patients before any treatment is given, including the targeted therapies, is totally crucial and really underlines the importance of patients reading the literature we give them, clinical nurse specialists in the clinic educating patients – that’s all so important because some of these side-effects are permanent, such as the endocrine side-effects, for example.”

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