Positive results from a clinical trial published today in The New England Journal of Medicine show that the combination of the immunotherapy drugs ipilimumab (Yervoy™) and nivolumab (Opdivo™), produced significantly better outcomes than ipilimumab alone in patients with advanced melanoma. A second piece in the same issue from MSK details a dramatic response occurring after a single dose of the combination therapy.
A research study led by medical oncologist Michael Postow and co-senior authored by MSK’s Jedd Wolchok, Chief of the Melanoma and Immunotherapeutics Service in collaboration with F. Stephen Hodi from Dana-Farber Cancer Institute, showed that the ipilimumab-plus-nivolumab combination produced significantly better outcomes than ipilimumab plus placebo in patients with advanced melanoma. The results from this phase ll double-blind clinical trial were presented at the American Association of Cancer Research Annual Meeting (AACR).
This trial included 142 patients with advanced melanoma who had not been previously treated. Of these patients, 109 had a normal form of the gene BRAF in their tumors and 33 had BRAF V600 mutations. Patients were randomly assigned to receive ipilimumab plus nivolumab, followed by nivolumab alone, or ipilimumab plus placebo, followed by placebo alone. Patients that were randomized to receive ipilimumab plus placebo initially could receive nivolumab later if ipilimumab alone was ineffective.
The response rate based on significant tumor shrinkage was 61 percent in patients receiving the combination therapy compared with 11 percent in patients receiving ipilimumab plus placebo. Patients receiving both drugs also lived longer without their disease progressing. Side effects of the combination therapy were more than those for patients receiving ipilimumab alone, but side effects were manageable.
“The incredibly high response rate seen in this trial for patients receiving the combination, approximately 60 percent now lets us tell patients that they have a high chance of significantly shrinking their melanoma with this treatment.” said lead author Michael Postow. “More research is still needed, however, to know if it is necessary to give all patients this combination or if patients should receive drugs like nivolumab and ipilimumab in sequence.”
“We are excited about these results and believe they support the principle that rationally combining effective medicines is an approach to achieving better outcomes for patients,” explained senior author Jedd Wolchok.
The US Food and Drug Administration approved nivolumab in late 2014. Memorial Sloan Kettering physicians helped spearhead clinical trials testing nivolumab’s safety and effectiveness and continue to conduct studies using the drug to treat melanoma and other cancers. In particular, MSK was one of the primary sites, led by Dr. Sandra D’Angelo for the multi-center phase III trial that directly led to the FDA approval, enrolling a large number of patients in the study.
In addition to this study, NEJM published a letter written by medical oncologists Paul Chapman, Sandra D’Angelo, and Jedd Wolchok that describe the remarkable effect of the ipilimumab-nivolumab combination in a single patient whose melanoma had returned after surgery. The patient had a large tumor under her breast, but a single treatment with the two drugs caused the entire mass to disappear in only three weeks.
”This is one of the most astonishing responses I have seen,” said medical oncologist Paul Chapman. “It reminds us of the potential power of the immune system if we can remove the “brakes” that keep it from attacking cancer cells.”