Over 16,000 Australians might be diagnosed with melanoma yearly. Most of them might be detected early and may be treated surgically.
However, for patients with advanced melanoma or metastatic melanoma that has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (attack specific features of the cancer) and immune therapies (that harness the immune system). Over the past decade, the variety of patients with advanced melanoma using these treatments has increased significantly survive for not less than five years after diagnosis, from lower than 10% in 2011 to roughly 50% in 2021.
While that is great news, there are still many melanoma patients who can’t be treated effectively with current therapies. Scientists have developed two exciting recent therapies which can be being evaluated in clinical trials in patients with advanced melanoma. Both require the use of immunotherapy at different times and in other ways.
The first results of this study are actually being made publicly available, providing insight into the way forward for melanoma treatment.
Immunotherapy before surgery
Immunotherapy works by increasing the strength of the patient’s immune system to help kill cancer cells. One sort of immunotherapy uses so-called “immune checkpoint inhibitors.”
Immune cells carry “immune checkpoint“proteins that control their activity. Cancer cells can interact with these checkpoints, turning off immune cells and hiding from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system lively in fighting cancer.
Results from an ongoing Phase 3 trial of immune checkpoint inhibitors were recently published in a journal New England Journal of Medicine.
This study used two forms of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.
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The study enrolled roughly 423 patients (many from Australia) and participants were randomly assigned to certainly one of two groups.
The first group underwent surgery to remove the melanoma after which received immunotherapy (nivolumab) to help kill the remaining cancer cells. Giving systemic (whole body) therapy, equivalent to immunotherapy, after surgery is: standard way melanoma treatment. The second group first received immunotherapy (nivolumab plus ipilimumab) after which underwent surgery. This is a brand new approach to the treatment of those cancers.
Based on previous observationsresearchers predicted that giving immunotherapy to patients while the tumor was still present could be rather more effective at activating the patient’s immune system’s ability to fight the cancer than giving it after the tumor had been removed.
Indeed, 12 months after starting therapy, 83.7% of patients who received immunotherapy preoperatively remained cancer freecompared with 57.2% in the control group who received immunotherapy after surgery.
Based on these results, Australian of the Year Georgina Long – who co-led the study with Christian Blank from the Netherlands Cancer Institute – suggested that this approach to pre-operative immunotherapy needs to be considered a brand new standard of look after high-risk stage 3 melanoma. She also said the same strategy needs to be evaluated for other cancers.
Promising results from this phase 3 trial suggest that this mix treatment could possibly be used in Australian hospitals over the next few years.
mRNA vaccines
Another emerging type of melanoma therapy is the postoperative combination of one other checkpoint inhibitor (pembrolizumab, which blocks PD-1) with a messenger RNA vaccine (mRNA-4157).
Although checkpoint inhibitors equivalent to pembrolizumab have been around for over a decade, mRNA vaccines equivalent to mRNA-4157 are a more moderen phenomenon. However, you could be aware of mRNA vaccines as biotech firms Pfizer-BioNTech and Moderna have released them Covid vaccines based on mRNA technology.
mRNA-4157 works in essentially the same way – mRNA is injected right into a patient and produces antigens, that are small proteins that train the body’s immune system to attack the disease (in this case cancer, or in the case of Covid-19, the virus).
However, mRNA-4157 is exclusive – literally. This is a sort of personalized medicine in which mRNA is created specifically for the needs of the patient’s cancer. First, the patient’s tumor is genetically sequenced to determine what antigens will best help the immune system recognize the cancer. A patient-specific version of mRNA-4157 is then created to produce these antigens.
The latest results of a three-year Phase II clinical trial combining pembrolizumab and mRNA-4157 have been published announced last week. Overall, 2.5 years after study initiation, 74.8% of patients treated with immunotherapy combined with mRNA-4157 were freed from cancer after surgery compared with 55.6% of patients treated with immunotherapy alone. These were patients affected by high-risk late-stage melanoma they typically perform poorly.
It is value noting that these results haven’t yet been published in peer-reviewed journals. They can be found as corporate announcements and have also been presented at some oncology conferences in the United States.
Based on the results of this study, pembrolizumab and vaccine combination therapy achieved: phase 3 trial in 2023, with first patients is registered in Australia. However, the final results of this study aren’t expected until 2029.
The hope is that this mRNA-based cancer vaccine will pave the way for vaccines targeting other forms of cancer, not only melanoma, especially when combined with checkpoint inhibitors that may help stimulate the immune system.
Despite continuous progress in the treatment of melanoma, the best way to fight cancer remains to be prevention, which in the case of melanoma means, every time possible, protection against exposure to UV radiation.