Global Melanoma Research Report
1 December 2016
Welcome to our first Global Melanoma Research Report – our quarterly update of selected research from around the world and here at Melanoma Institute Australia (MIA) that is making a difference to the lives of melanoma patients now and in the future.
Preventing advanced melanoma with adjuvant therapy
Patients with resected lymph node positive (Stage III) melanoma have a high risk of developing distant recurrence (Stage IV). Multiple previous attempts to prevent this with adjuvant (post-operative) drug treatments have been unsuccessful. This year, for the first time in a clinical trial, researchers from MIA and their international collaborators have shown a clear reduction in the risk of recurrence and an improvement in survival with adjuvant ipilimumab (Yervoy®). Consequently, melanoma doctors are excited.
“This is the biggest practice-changing moment of this year,” says MIA’s medical oncologist Dr Alex Menzies of the paper that was published recently in NEJM. “This is the first time in treating melanoma that we’ve ever had an effective adjuvant therapy that improves overall survival.”
The trial found that as an adjuvant therapy for high-risk Stage III melanoma, ipilimumab prevented relapse and improved survival compared to placebo, reducing the risk of death by 28%.
“However, it comes at a big cost as it has many side effects,” warns Professor Grant McArthur from Peter MacCallum Cancer Centre. “There is a follow-up trial underway to vary the dose of ipilimumab to see if we can give it at a lower dose to reduce the side effects and still be effective. These results are eagerly awaited.”
Trials are also underway using other newer and better immunotherapies (eg, anti-PD-1 antibodies) and targeted therapies (e.g. BRAF and MEK inhibitors) in the adjuvant setting, all of which are being run at MIA.
“This trial gives us great hope that the drugs we currently have in the metastatic setting will have similar benefit in the early stage setting,” says Dr Menzies. “MIA has been instrumental in the development of new drugs that have now raised the bar in the metastatic setting, and now we are playing a pivotal role in trying to improve the treatment of early stage melanoma.”
Nivolumab improves quality of life in patients with advanced melanoma
Together with an international team of collaborators, researchers at MIA have found that nivolumab (Opdivo®) not only improves survival but can also improve quality of life in patients with advanced melanoma. These findings came from the clinical trial known as CheckMate-066 – a phase 3 clinical trial evaluating the efficacy of nivolumab in advanced melanoma.
“[This confirms] the superior benefit of nivolumab over dacarbazine in terms of not only survival, but also quality of survival from the patient’s perspective,” wrote Professor Georgina Long from MIA. “These results suggest that patients receiving nivolumab for melanoma can expect to maintain their quality of life throughout treatment.”
This research was published in Annals of Oncology.
Mechanism behind BRAF-mutant resistance to therapies is identified
Some melanoma treatments stop tumour growth by inhibiting the BRAF gene, but many patients develop resistance to the therapies and tumours reoccur. Our collaborators from Massachusetts General Hospital have identified a previously unknown mechanism that allows BRAF-mutant melanoma cells to resist targeted therapies.
Being able to predict response to BRAF inhibitor drugs (eg. vemurafenib and dabrafenib) will help to identify early patients who are likely to benefit from treatment and enable monitoring of the development of resistance, which would allow consideration of other treatment options prior to relapse.
The study was recently published in the journal Nature Medicine.
Specialised surveillance clinics would improve health outcomes for Aussies at very high risk of melanoma
Early detection of melanoma is crucial for saving lives and current guidelines advise “regular monitoring” to ensure melanoma is caught early. However, until now, it had not been proven how often this should be done and what the costs and benefits would actually be in practice.
A specialised “High Risk Clinic” to monitor people at very high risk of developing melanoma was found to be effective in managing high risk individuals but cost-effectiveness was unknown. This specialised surveillance clinic examines people every six months, photographs and maps their moles via total body photography, and uses close-up sequential digital photography to observe any changes over time.
“Our research has shown that for people at highest risk, close monitoring would save more than $6,800 per patient over 10 years,” says lead author Dr Caroline Watts, from MIA and The University of Sydney. “Fewer suspicious moles would be unnecessarily cut out, and the early detection of melanomas would mean less extensive surgery would be required.”
The research, published in JCO, is likely to lead to calls for new rebates in the Medicare Benefits Scheme to support access to regular monitoring using total body photography and close-up digital imaging.
Using clinical features to identify patients at high risk for melanoma
Can an individual’s risk factors for melanoma be used to tailor skin self-examinations and surveillance programs? A new study published by JAMA Dermatology suggests they could by identifying those patients at higher risk who may benefit from increased surveillance.
MIA’s Dr Caroline Watts and colleagues examined clinical features associated with melanomas according to patient risk factors (many moles, history of previous melanoma and family history of melanoma) to improve the identification and treatment of those at higher risk.
“The results of our study suggest that a person’s risk factor status might be used to tailor their surveillance program in terms of starting age and education about skin self-examination or more intensive surveillance,” the study concludes.
Reducing fear of melanoma recurrence in high risk patients
More than 70% of melanoma survivors report high levels of fear needing psychological support, however limited psychological support is available for patients.
A new psychological intervention study published in JCO and co-authored by MIA has been shown to significantly reduce melanoma survivors' fear of their cancer returning.
The intervention halved the number of patients who had a fear of cancer recurrence that would require treatment. The intervention combines three telephone-based psychotherapeutic sessions, delivered by trained psychologists, with a comprehensive psycho-educational booklet called Melanoma: Questions and Answers.
It is hoped that this type of work will change the way clinicians look at their patients, moving towards a more holistic approach.