By Louise Perkins, Ph.D.
Chief Science Officer
The world of melanoma has changed dramatically in a way one might not have envisioned in 2011. How can you tell? From the stories of patients and their caregivers. A common story can go like this: Just diagnosed with Stage 4 melanoma. Need to select the best treatment approach sooner than later. Many options to choose from. What questions should they ask the doctor?
In 2008, when MRA’s first grants were made, no one would have imagined we’d be talking about how to choose among so many treatments for patients. The pace of change has been fast and furious since 2008, and it’s picked up steam in 2014 and 2015.
In less than 5 months, there have been 5 new treatment approaches approved by the FDA. Think about that for a minute! This pace of treatment change is beyond unprecedented and includes a number of “firsts.” What were these changes and what does it mean for patients?
“Firsts” for Melanoma in 2015:
- The first combination immunotherapy – ipilimumab and nivolumab – approved
- Nivolumab is approved as a first line of treatment, marking the first anti-PD-1 immunotherapy drug for previously untreated BRAF wild-type melanoma
- T-VEC, an oncolytic viral therapy that’s directly injected into a tumor, is the first of its kind treatment to be approved
- Vemurafenib and cobimetinib is approved by the FDA, the first melanoma combination approval that includes a never-before-approved drug
- Ipilimumab is approved for adjuvant treatment, the first checkpoint inhibitor drug approved in the adjuvant setting
- Pembrolizumab is approved as a first line of treatment for metastatic melanoma regardless of a patient’s BRAF status – the first anti-PD-1 therapy to receive such designation
All of these ‘firsts’ should give you a sense of the true innovation in new treatment approvals that melanoma is spearheading with the help and support of patients, doctors, companies, and the FDA. These offer good options for patients as they pick their Plan A.
So, patients should always be thinking about Plan B in discussion with their doctors. Why? Because cancer is tricky, and it sometimes roars back just when it seems like it’s been beaten. In addition to that, not all patients respond to immunotherapy or targeted therapy. Others simply can’t tolerate the treatments and have to be taken off for their own safety. This means we still need different options to battle this awful disease.
What’s Needed for Melanoma Research?
New studies are underway that address two main needs:
- How to use the drugs we have now in better ways, either alone or in combination
- Defining the biology of difficult-to-treat disease and figuring how that knowledge can be used to find new targets and treatments
Fine-tuning the drugs we have
Finding the optimal order by which to give treatments (e.g. Drug A then Drug B or Drug B then Drug A or Drug A and B at the same time) remains key if we are going to maximize the utility of these existing miraculous treatments. The field needs to think broadly about cause and effect of using various drugs, their impact on cancer cells, the immune system and the body as a whole especially as it relates to having drugs work in otherwise resistant melanomas.
Tackling difficult-to-treat melanoma
It is becoming increasingly clear that altered signals inside the cell that flow through a node called ERK are important in the vast majority of melanomas. The presence in half of melanomas of BRAF mutations that ultimately activate ERK provided the first clue that this was important. Further studies are showing that a panoply of alterations turn ERK signaling on even in the absence of activated BRAF. This highlights the need to more effectively target ERK signaling and resistance to such inhibition. And new ways to stimulate the immune system would be a plus, too. All of this is the sort of research that MRA has supported and continues to as much as possible.
Making a long story short, there is an overriding need for continued innovation. Too many patients are not benefiting from these new therapies, and we have to ensure that new targeted and immunotherapy approaches are invented and tried – based on sound science. What are the next new immune therapies? New signaling inhibitors? Is there a critical mass of info that can form the basis of the next leap in progress? This is where we need to push.