MIA takes centre stage at leading cancer conference

5 June 2019

Researchers from Melanoma Institute Australia (MIA) took centre stage at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, attended by over 40,000 professionals. Results presented by MIA’s contingent have the potential to create better patient outcomes and change the way advanced melanoma is treated.

Four independent presentations on melanoma were given by MIA researchers at the world’s leading oncology conference, and a highly prestigious Clinical Sciences Symposium was presented in the Next Generation Therapeutics and Biomarkers session by postdoctoral researcher Dr Inês Da Silva.

“Four presentations from one institution, including a Clinical Science Symposium, is unprecedented. These presentations will change the way we treat melanoma patients, as well as their quality of life,” said MIA’s Co-Medical Director, Professor Georgina Long.

Dr Da Silva’s research is paving the way for personalised therapies, as she unveiled a detailed analysis of melanoma biomarkers to predict treatment response. Currently, biomarkers for response to immunotherapy have been studied in isolation. Dr Da Silva looked at a range of characteristics of patients and their melanoma and how these interact to create a multivariate predictive model. Her research found that high levels of two molecular factors – tumour mutational burden and interferon gamma – are predictive of good response to immunotherapy and longer progression-free survival in patients with metastatic cutaneous melanoma. Importantly, Dr Da Silva focused on patients who are ‘outliers’ – those who do not have these features who responded to therapy, or those who have these features who did not respond. Looking closely at what makes these patients different could prove crucial in our understanding of resistance and help us find treatments that will work for patients who currently don’t respond.

“These outliers are so important to our research. These are the patients who can teach us about resistance or conversion to therapy, which is our next big research focus,” said Professor Richard Scolyer, Co-Medical Director of MIA.

Another MIA presentation outlined what researchers hope will be the new benchmark for drug testing and regulatory approval. MIA’s Associate Professor Alex Menzies presented analyses of data from six neoadjuvant clinical trials on behalf of the International Neoadjuvant Melanoma Consortium (INMC). Neoadjuvant immunotherapy, where a drug is given prior to surgery then continued afterwards, shows early promise as the new standard of treatment with evidence suggesting it may be more effective in melanoma patients. The data suggests it could act as a possible early marker of long-term survival. This is determined by the patient’s pathological response rate, which is identified through a biopsy. To date, no patient in any of the trials with a complete pathological response has shown disease progression at all throughout two years of follow-up. Due to this success, the INMC is developing a ‘Master Protocol’ for neoadjuvant clinical trials to standardise trial design, pathological assessment, and translational research. This will allow new drugs to be compared with current standard-of-care in a quick and efficient way, leading to the possibility of quicker approvals for drugs that show therapeutic benefit.

MIA medical oncology fellow Dr Carina Owen presented the analysis from her study looking at international data of patients who recur on adjuvant immunotherapy (immunotherapy given after surgical intervention). Her analysis reveals that patients who recur after stopping treatment early or completing their therapy may respond to further immunotherapy. This is termed salvage therapy and has the potential to open further lines of treatment and longer survival for these patients. Most patients who recur, however, will recur early while on treatment. These patients are resistant to therapy, and none of the patients analysed in this study responded to subsequent therapy. This underscores the need for more research and further clinical trials to cater to these resistant patients – the next phase of MIA’s research focus.

Professor Angela Hong also presented the results from MIA’s whole brain radiotherapy (WBRT) trial. The international Phase III trial found that WBRT does not prolong overall survival compared to observation. As WBRT can be morbid, using this information as the foundation for treatment changes will improve the quality of life for patients whose melanoma has spread to the brain.

In the melanoma and skin cancer poster session, MIA was again well-represented with six posters on display. Professor Long presented two posters summarising new and further results from clinical trials. The newest cohort of patients on the Keynote-029 study have been analysed, and it was found that the combination of pembrolizumab and ipilimumab given in a new dosing schedule is effective and safe, with more follow-up to come. The continuing Combi-I trial has been analysed for updated safety and efficacy, showing promising durability of response with manageable toxicities.

A poster by Dr Inês Da Silva described a model to predict response to immunotherapy. Importantly, the best predictors of response are routinely collected clinical factors, easily accessible through a blood test, making this a practical and inexpensive tool to help guide clinicians in making treatment choices for their patients. PhD student Dr Jenny Lee presented a poster on the use of circulating tumour DNA (ctDNA) as a biomarker for the presence and monitoring of melanoma brain metastases. While she found that ctDNA was not a useful biomarker for the status of brain metastases, it is till a useful tool for determining extracranial response.

Associate Professor Matt Carlino presented the outline of a new clinical trial, where giving patients with resected Stage II melanoma adjuvant pembrolizumab will be compared with the current standard of care, observation. Finally, clinical trials manager Maria Gonzalez presented a poster summarising MIA’s new ABC-X clinical trial, aided by funding from Jay’s Longest Melanoma March. This trial will combine radiotherapy with immunotherapy in patients with brain metastases to determine if this will increase the effectiveness of the treatment.

“We’re exceptionally proud of our ASCO presenters. Each one is pushing forward the treatment landscape for our patients and edging closer to our goal of zero deaths from melanoma,” said Professor Long.

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