Global Melanoma Research Report - July
20 July 2017
Welcome to our quarterly update of selected research from around the world and here at Melanoma Institute Australia (MIA).
Practice-changing research to reduce surgery
New findings from a large international clinical trial are likely to change the way melanoma is managed in many patients by reducing the need for major surgery and its associated morbidity and cost.
Melanoma management guidelines currently state that patients who are found to have melanoma deposits in a “sentinel” lymph node should undergo immediate completion lymph node clearance — a large operation that removes all remaining lymph nodes in the area (the axilla, the groin or the neck).
However, the initial results of the second Multicenter Selective Lymphadenectomy Trial indicate that there is no difference in survival for sentinel-node positive patients who undergo immediate lymph node clearance compared to those who instead are closely monitored with ultrasound to detect disease progression. MIA was the top recruiter of patients to this international trial.
“This change in treatment recommendation is likely to improve the quality of life for many patients around the world,” said co-author and Senior Surgeon at MIA, Professor John Thompson AO.
This research was published in New England Journal of Medicine.
Identifying markers for optimal response
Researchers are trying to identify biomarkers that correlate with treatment benefit to optimise treatment for patients. There has been a lot of excitement around circulating tumour DNA (ctDNA) that can be found in a simple blood test and be used to identify, with high sensitivity, genetic mutations that indicate the presence of melanoma cells in the body.
New research from MIA has found ctDNA is an accurate predictor of tumour response, progression-free survival and overall survival in melanoma patients receiving PD-1 inhibitors.
This research was published in Annals of Oncology.
More accurately predicting survival for melanoma patients
Staging guidelines are used to determine a patient’s prognosis. However, they only provide information to establish a prognosis at initial diagnosis and none thereafter. Research by MIA has now provided this missing information by developing conditional survival estimates for Stage III melanoma patients which enable more accurate predictions of survival outcomes.
Using the vast database of patients in MIA’s Melanoma Research Database (known as MRD2), which details the patient’s clinical information and outcomes, researchers now have more accurate estimates of survival that can guide patients and their doctors with subsequent follow up and treatment decisions. Given the recent introduction of effective immune and targeted systemic therapies, and results soon to be presented regarding their efficacy in Stage III, refining the staging system for patient subgroups is crucial.
This research was published in Journal of Clinical Oncology.
Whole genome sequencing finds unexpected genomic landscape in melanoma
By looking at the ‘dark matter’ of the genome, new research from MIA has found that genetic changes in acral and mucosal melanoma are completely different to mutations found in skin melanoma.
The study found that genetic changes in melanomas on the hands and feet (acral) and internal surfaces (mucosal) are completely different to the mutations found in skin melanoma. This confirms them as very distinct diseases from each other and opens the door to develop more effective treatments.
This research was published in Nature.
A new era for melanoma patients with brain metastases
Melanoma patients often develop brain metastases, and until recently, most patients with brain metastases only lived for a few months. Data was presented at the ASCO conference this year from three clinical trials in patients with asymptomatic brain metastases who had not previously received local therapy (e.g. surgery, radiotherapy). The research demonstrated that modern melanoma drugs shrink brain metastases and prolong survival. This offers great hope to melanoma patients and changes current clinical practice.
The COMBI-MB trial of the targeted therapies dabrafenib and trametinib, demonstrated impressive response rates and superior survival to what has been seen previously. While most patients had shrinkage of brain metastases initially, most then became resistant to treatment after only a few months, such that only a few patients had long-term disease control. This resistance phenomenon, also seen in patients without brain metastases, remains a barrier and research continues to identify why this occurs and to prevent it.
In contrast, two trials of immunotherapy, MIA’s ABC clinical trial and the CheckMate 204 trial, demonstrated not only a high rate of response but also durable survival with a combination of nivolumab and ipilimumab. These impressive results, similar to those seen in patients without brain metastases, indicate that some patients may not necessarily need to undergo surgery or radiotherapy to the brain, and that they may have long-term survival with drug therapy alone. The only caveat is that those who progress at 12 weeks — approximately a third of patients — have no benefit at all.
Pembrolizumab and response
New research has examined why some melanoma patients on pembrolizumab (Keytruda) respond to treatment while others do not. They found that patients who didn’t respond to treatment had an imbalance between the size of their tumour and how exhausted their immune cells were.
Matching the size of a tumour to the body’s immune response could help doctors tailor immunotherapy treatments for melanoma patients whose disease has spread, according to a small US study.
This research was published in Nature.