Wednesday, December 9, 2015
- Melanoma is a type of skin cancer that can spread to other organs, including the brain.
- Immunotherapy drugs like the one Mr. Carter received are offering new hope to patients with metastatic melanoma.
- Combination treatments may improve outcomes for some patients.
Update: The immunotherapy drug that helped President Carter beat back cancer is yielding even more encouraging results. Data released on May 18, 2016 in advance of the annual meeting of the American Society of Clinical Oncology indicate that 40% of patients who received pembrolizumab (Keytruda®) as part of a large clinical trial are still alive three years later — a huge improvement over just a few years ago when average survival time for patients with metastatic melanoma was measured in months.
This week, former President Jimmy Carter announced that he is “cancer free” after receiving treatment for metastatic melanoma — a type of skin cancer that often spreads, or metastasizes, to other parts of the body. Mr. Carter’s cancer was discovered in his liver and spread to his brain.
In addition to surgery and radiation, Mr. Carter received a new immunotherapy drug called pembrolizumab (Keytruda®), which releases a brake on the immune system, empowering it to mount a stronger attack against cancer. The particular braking molecule targeted by this drug is called PD-1.
To get a better sense of what Mr. Carter’s surprise announcement means — especially for patients in a similar situation — we spoke with Jedd Wolchok, Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering.
Mr. Carter received three types of cancer treatment: surgery, radiation, and immunotherapy. At this point, can we say which was most responsible for his cancer-free outcome?
That’s a great question. My colleagues and I were just discussing this. I think it’s probably a contribution from all of the above. I don’t think it’s possible to ascribe the very favorable result to just one intervention. As time goes on, if he continues to have durable control of his disease, then I think we can be confident that immunotherapy played an important role.Back to top
Can the combination of radiation and immunotherapy work together in a synergistic way to provide added benefit to patients?
There is that possibility. The hope is that when you kill a tumor with a tool like radiation therapy, you release cell debris that can trigger an immune response — similar to a kind of vaccination. Then, by blocking an immune checkpoint — in this case PD-1 — you allow that immune response to really take off.
We’ve certainly seen isolated examples of this phenomenon, called the abscopal response, with other immunotherapy drugs. I wrote a paper about this a couple of years ago with my MSK colleague Michael Postow. We’re now about to open a study using a combination of two immunotherapy drugs, ipilimumab and nivolumab, along with radiation for patients with melanoma. A lot of folks are really interested in this, and you can build a strong rationale for why it makes sense to use them together. But it has to be tested.Back to top
Are there times when it’s not possible to receive immunotherapy because of brain metastases?
We have a lot of issues yet to settle here. We know that the same medicines that can have a favorable effect on disease outside of the brain can have a favorable effect in the brain. There was a clinical trial that I participated in and published in Lancet Oncology about two years ago that looked at ipilimumab treatment in melanoma patients with brain metastases.
The challenge with brain metastases is that sometimes patients require corticosteroid treatments [which can suppress the immune system] to control swelling and symptoms. In the trial I referred to, the benefit of ipilimumab was seen only in the patients who were able to come off corticosteroids. So that’s an important consideration.
That’s why it’s good to do exactly what Mr. Carter’s physicians did, which was to control the brain metastases to the best of their ability — in this case with stereotactic radiosurgery — get him off the steroids as quickly as possible, and then initiate the immunotherapy.Back to top
Is Mr. Carter’s experience representative of patients with metastatic melanoma and brain metastases?
It’s becoming more and more common. Mr. Carter’s case is a great example of how far the field has come in a relatively short period. If you turn back the clock ten years or so, people with melanoma and brain metastases had life expectancies that were measured in weeks and months. Now, there are patients in my practice who have had brain metastases and have been alive for years. And of course we hope the same is true for Mr. Carter.
I find it very inspiring that he’s been able to continue the important work that he’s engaged in without any side effects from treatment.
It’s also inspirational to patients, who can see that a devastating diagnosis doesn’t necessarily mean that you’re going to die immediately, or that the treatment is going to incapacitate you. Here’s a 90-year-old person not just living but fully active and engaged in activities that are making the world better for the rest of us.
Pembrolizumab is one of two PD-1-blocking drugs approved by the FDA for the treatment of advanced melanoma, the other being nivolumab (Opdivo®). The five-year survival rate for patients treated with nivolumab is 34%, as reported last month at the annual meeting of the American Association for Cancer Research. Check back here on the MSK blog for more updates on progress in immunotherapy.Back to top