By Louise Perkins, PhD
Chief Science Officer
There’s been a lot of news on melanoma treatments in the last couple of weeks coming out of the two largest cancer conferences held each year: the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) annual meetings. The results – particularly in the area of immunotherapy – really are exciting for the field of melanoma and cancer, at large. On the Diane Rehm Show this week, melanoma was described as the “poster child for immunotherapy,” which it certainly has been.
So what’s new, and what does it mean now and for the near future?
Melanoma drugs circa 2014
In September and December 2014, two new melanoma treatments were approved by the FDA for advanced metastatic melanoma. These are the anti-PD-1 drugs pembrolizumab (pembro, Keytruda®) and nivolumab (nivo, Opdivo®). Pembro and nivo release the so-called “brakes” on the immune system, to help the body’s own immune system fight cancer. Another drug, ipilimumab (ipi, Yervoy®), is an anti-CTLA-4 drug and was FDA-approved in 2011. Check out our video that describes how these immunotherapies work.
The latest news from early 2015
Researchers have been trying to answer a few important questions about these new immunotherapies, such as:
- Is anti-PD-1 (pembro, nivo) treatment better than anti-CTLA-4 (ipi) in patients who have not had any prior therapy?
- Do anti-CTLA-4 and anti-PD-1 in combination work even better than either treatment alone for patients who have not had any prior therapy?
MRA-funded investigator Jedd Wolchok, MD, PhD, and colleagues addressed the latter question in a Phase 3 trial at ASCO. The study involved more than 900 previously untreated metastatic melanoma patients and compared three different therapies:
- Ipi alone
- Nivo alone
- Ipi and nivo in combination
They found that nivo either alone or in combination with ipi had better results for patients than ipi alone.
This is similar to what was reported at AACR by Antoni Ribas, MD, in a Phase 3 study of the other anti-PD-1 drug pembro, which showed that pembro was better than ipi in previously untreated patients. More trials are underway to confirm whether or not the combination allows patients to live longer (overall survival) versus single-agent therapy.
One important piece to note is that recent studies found that the increased benefit of the combination also comes with increased side effects; in fact, approximately one-third of patients discontinued therapy due to side effects.
At ASCO, Michael Atkins, MD, summarized these clinical findings that have been presented over recent months:
- Nivolumab is better than ipilimumab alone
- Pembrolizumab is better than ipilimumab alone
- Nivolumab and ipilimumab in combination are better than ipilimumab alone
What does this mean for melanoma patients?
Believe it or not, things are moving amazingly fast. So what does all of this mean for patients in June 2015, just 9 months after the first anti-PD1 treatment was approved by FDA? Well, one leading cancer guideline group, the National Comprehensive Cancer Network, already updated its melanoma treatment guidelines in March to recommend that oncologists consider a single-agent anti-PD1 (either nivo or pembro) as first line treatment for advanced metastatic melanoma patients (pembro and nivo were FDA approved for patients who have progressed on prior therapies).
More research is needed to determine if and when and for which patients the combination of anti-PD-1 and anti-CTLA-4 should be used.