Friday, May 8, 2015
A clinical trial showed that giving melanoma patients a combination of two immunotherapy drugs, ipilimumab and nivolumab, resulted in significantly better outcomes than treating them with ipilimumab alone. One patient even had a grapefruit-size tumor disappear in weeks after a single treatment. Both drugs work — in slightly different ways — by removing a natural brake on the immune system.
- Melanoma patients were given two immunotherapy drugs together.
- The drugs were ipilimumab and nivolumab.
- The two-drug combination worked better than ipilimumab alone.
- This could be a significant advance in melanoma treatment.
Excitement continues to grow about new treatments that unleash the immune system to destroy cancer cells. In particular, great promise is being shown by immune checkpoint blockade (ICB) therapy — a class of drugs that boost the cancer-fighting powers of immune T cells, a type of white blood cell, by blocking certain receptor molecules on the cells’ surface.
MSK has played a leading role in developing this approach and testing these drugs, which include ipilimumab (Yervoy™), nivolumab (Opdivo™), and pembrolizumab (Keytruda™). The therapies have produced remarkable results, eliminating cancer completely, as judged by scans, in some patients with highly advanced melanoma.
Now, two related reports by MSK researchers in the New England Journal of Medicine show that giving two of these drugs together can dramatically increase their effectiveness.
“Incredibly High Response Rate”
One study showed that giving both ipilimumab and nivolumab produced significantly better outcomes than ipilimumab alone in patients with advanced melanoma. The researchers tested the two-drug combination in 142 patients with metastatic melanoma who hadn’t yet received other treatment. The response rate — based on tumor shrinkage — was significantly higher in the patients receiving the combination therapy (61 percent) compared with patients receiving ipilimumab plus a placebo (11 percent).
The effect of the combination therapy also proved more durable, as patients receiving both drugs survived longer without their disease progressing. Those receiving the combination therapy were more likely to have side effects (54 percent) than those receiving ipilimumab plus placebo (24 percent), but these side effects were manageable.
“The incredibly high response rate seen in this trial for patients receiving the combination therapy now lets us tell patients that they have a high chance of significantly shrinking their melanoma with this treatment,” says MSK medical oncologist Michael Postow, the report’s first author. “More research is 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,” adds medical oncologist and immunologist Jedd Wolchok, who led the study together with Stephen Hodi, an immunologist at the Dana-Farber Cancer Institute in Boston.
The US Food and Drug Administration has approved ipilimumab and nivolumab separately as melanoma drugs but has not approved their combined use. More study is needed to see whether patients receiving the combination therapy ultimately live longer. Future trials also could help researchers determine the optimal number of treatments to be effective while minimizing side effects.Back to top
Large Tumor Dissolves after Single Treatment
In addition to this study, NEJM also published a letter written by Dr. Wolchok and medical oncologists Paul Chapman and Sandra D’Angelo describing the remarkable effect of the ipilimumab-nivolumab combination in one patient whose melanoma had returned several years after surgery. The woman had a grapefruit-size tumor under her breast, but a single treatment with the two drugs caused the entire mass to disappear in only three weeks, leaving a cavity.
“This is one of the most astonishing responses I have seen,” Dr. Chapman says. “It reminds us of the potential power of the immune system if we can remove the brakes that keep it from attacking cancer cells.”
The researchers write that the potent effect illustrated by this single case also raises possible safety concerns. While no such problems have been reported thus far, Dr. Chapman notes that in rare cases, very quick tumor shrinkage could lead to complications. For example, a sudden hole in the heart muscle — a common site for metastatic melanoma — could hypothetically lead to bleeding.
“The irony that we are now concerning ourselves with an overly vigorous anti-melanoma response has not gone unnoticed,” he adds.Back to top