Highlights in melanoma research from ESMO
21 September 2017
The European Society for Medical Oncology (ESMO) Congress recently held in Madrid, Spain, provided a platform for announcing a number of key melanoma research findings. Some 24,000 oncology health professionals from 130 countries attended the conference, including Melanoma Institute Australia's medical oncologist Dr Alex Menzies who presented ground-breaking research lead by MIA.
Dr Menzies’ presentation was one of several detailing results from key clinical trials which will change how melanoma is treated around the world.
Adjuvant trial results transforming patient care
The highlight of the conference this year was MIA's research demonstrating that we now have effective adjuvant therapy for high-risk Stage III melanoma patients. Until now, these patients whose melanoma had been resected were at a high risk (40−70 per cent) of their disease progressing to metastatic melanoma, yet they simply had to play the waiting game to see if their disease would spread to distant organs.
Results from the two international clinical trials were presented in late-breaking abstracts at ESMO and simultaneously published in the New England Journal of Medicine.
“In the COMBI-AD trial where we used targeted therapies, we saw a 53% reduction in the risk of melanoma recurrence and a reduction in death of 43%,” said Dr Menzies. “In the CheckMate 238 trial, we saw a 35% reduction in the risk of recurrence on nivolumab compared to ipilimumab, a drug already shown to reduce recurrence and improve survival compared to observation.”
“These are game changing results that we will change the way we treat melanoma patients and which will ultimately save lives,” he commented. “This means that we’ll soon have standard therapy available for Australian patients with high-risk melanoma.”
Neoadjuvant trial of targeted therapy
Dr Menzies presented findings from our Phase II neoadjuvant trial of targeted therapy in Stage III patients. The trial tested a combination of dabrafenib and trametinib given before and after surgery in patients with resectable Stage IIIB/C BRAF V600-mutant melanoma.
The study found that nearly half of all patients achieved a complete pathologic response by the time they underwent surgery, and that every patient had some degree of tumour shrinkage while on therapy. In almost half of the cases, surgery was deemed easier as well.
“These are patients who otherwise would just have surgery and then have observation,” Dr Menzies told OncLive in a recent interview. “And these are patients who are at very high risk, probably the highest risk, of recurrence without further therapy.”
The study concluded that neoadjuvant dabrafenib and trametinib has a high response rate in patients. Although no patient progressed during the neoadjuvant period of treatment, just over a third of patients did recur in the year after surgery (median follow up of 12.1 months).
“Despite half the patients having a complete response (no melanoma left at time of surgery), we are seeing recurrences during follow up,” he said. “They seem, at this stage, to be occurring just as often in patients who had a complete response as those that didn't, and it seems like the recurrence-free survival is similar in those two groups as well. What we question is that, at the end of the day—when we get to five years—are there just as many people in whom the melanoma has come back and died that received targeted therapy or not?”
Further follow-up is awaited, and MIA has begun trials of immunotherapy and combined targeted and immunotherapy in this setting.
Combination pembrolizumab and epacadostat
Other research presented at ESMO that is attracting global attention includes the findings from the Phase I/II study of combination pembrolizumab and the investigational IDO1 inhibitor, epacadostat, in advanced melanoma patients.
The results from the ECHO-202/KEYNOTE-037 trial demonstrated that the combination had a response rate in 55% of patients and disease control was seen in more than 70% of patients. The progression-free survival at 18 months for treatment-naïve patients was over 50%.
In addition, this combination of treatment was very tolerable and without any significant toxicities. Combination therapy often compounds side effects, but this study revealed that this combination creates toxicity comparable to single-agent pembrolizumab.
“This therapy is very translatable into the community,” said study author Dr Omid Hamid from the Angeles Clinic & Research Institute in a recent interview with OncLive. “It’s easy to give and has less toxicity than combinations that are approved at this point.”
“These results are looking very promising,” commented MIA’s Dr Menzies. “However, these trials were conducted in a small number of patients. We look forward to getting more robust results from the Phase III trial that MIA is involved in.”
A small subgroup analysis has also demonstrated that patients who are positive for PD-L1 receive extra benefit of epacadostat.
“If we see this effect replicated in the Phase III study, it could suggest that this combination could be ideal in the PD-L1 positive patients, whereas combination ipilimumab and nivolumab could be ideal in PD-L1 negative patients,” commented Dr Menzies.