Challenges in melanoma clinical research: A snapshot from the Australasian Melanoma Conference 2016

Challenges in melanoma clinical research

5 December 2016

The last decade has seen a surge in therapeutic options for advanced melanoma patients, thanks to research. However, not every patient responds to treatment and researchers are taking on the challenge to find out why.

Research presented at the recent Australasian Melanoma Conference in Sydney discussed the latest findings from clinical trials and labs around the globe. Hosted by Melanoma Institute Australia (MIA), the conference brought together 400 clinicians, researchers, nurses and students to discuss the multidisciplinary management of melanoma and showcase research innovation that is working towards personalised medicine for melanoma patients.

There have been unprecedented improvements in survival of patients with Stage IV melanoma, with one-year survival rates increasing from 25% with chemotherapy to now 75% with some treatments; but sadly not all patients are sharing this outcome. Our researchers are working towards our goal of zero deaths from melanoma, but we have many hurdles to overcome before we get there.

Here are some of the challenges facing melanoma researchers that were highlighted in new data and discussion at the conference:    

Deciphering the best order of treatment

We have two major types of treatment: one targeted against driver mutations and one working with the immune system. Some lab studies indicate that the two kinds of therapy could work against each other, or work better, depending on the order in which treatments are given. We really don’t know and this needs investigation. MIA will soon commence a neoadjuvant trial to see what sequence of targeted therapies and immunotherapies works best.

Understanding the ideal treatment combinations

We know that combining different types of targeted therapies improves clinical outcomes and prevents the development of resistance, although this often also results in an increase in severe side effects. However, we need to know how to combine targeted therapies with immunotherapies to get the best response with the least toxicity. There are clinical trials underway at MIA to address this question definitively.

Preventing recurrence

Adjuvant therapy is treatment given to a patient after the primary tumour is resected that aims to prevent the melanoma from coming back by killing melanoma cells hidden elsewhere in the body. Recently released clinical trial data revealed that giving the immunotherapy ipilimumab (Yervoy®) after surgery is likely to prevent melanoma recurrence in people with melanoma that has spread to lymph nodes (Stage III). This finding is likely to change the options available to everyone with Stage III melanoma and offers hope that other immunotherapies currently in trial will also be successful in this setting [find out more].

Predicting treatment outcomes

As patients’ responses to treatment are variable, researchers are trying to find markers to predict how they will respond to therapy to ensure the best possible treatment is given and to help predict the course of disease. This push towards personalised medicine will optimise treatment outcomes and reduce unnecessary side effects for patients.

Researchers have identified a number of potential markers to help predict response to treatment. But interestingly, it appears that it’s not just what to look for, but when that is important. Research presented by keynote speaker A/Prof Jennifer Wargo showed that an immune-activation signature, which is a biomarker of better survival in tumour biopsies taken before treatment starts, largely failed to predict if immune therapy (like anti-PD-1) would work or not. However, immune signatures in biopsies taken during treatment were a good early indicator of how a patient will respond to this kind of immunotherapy.

Improving response to treatment by modifying gut bacteria

There is emerging evidence that the gut microbiome, ie, its microbial flora, influences how well a patient responds to immune treatment. By comparing the gut bacteria of melanoma patients who responded to immunotherapy and those who did not, researchers found a stark contrast in the balance of bacterial species in the faecal samples of responding and non-responding patients.

“It is quite likely that we will modify the microbiome to enhance responses to therapy in the upcoming months and years,” said A/Prof Wargo.

Finding treatments for mucosal and uveal melanoma

Mucosal (internal body surface) and uveal (eye) melanomas are very different diseases from cutaneous melanoma (on the skin). They are caused by different gene mutations, are not linked to sun exposure, and respond differently to treatment. They have a very low response rate to immunotherapy and there is no current standard best option. More research and trials are desperately needed to improve this state of affairs.

To address this need in patients with uveal melanoma, MIA is running two new clinical trials investigating novel treatments for patients with metastatic uveal melanoma. The Phase I study of a new and exciting targeted treatment for uveal melanoma, led by Dr Matteo Carlino at Westmead Hospital in affiliation with MIA, is currently recruiting [find out more]. There will also be a Phase III trial commencing at MIA in early 2017 to compare immunotherapy and chemotherapy.

 

The Australasian Melanoma Conference was an excellent opportunity for those in the field of melanoma to converge, share their findings and ideas. By MIA bringing together and showcasing the great minds of melanoma, clinicians were able to learn from the best about the latest advances in melanoma research that will ultimately help their patients. Researchers were able to network and build upon each other’s progress, which will ultimately enable their research to push the boundaries even further. Although there are many challenges still to be faced by our researchers, our understanding of melanoma is continuing to progress at a rapid rate, which will boost outcomes for melanoma patients.