Landmark Melanoma Study Bears Out the Success of Combination Immunotherapy

MSK medical oncologist and immunologist Jedd Wolchok

MSK medical oncologist and immunologist Jedd Wolchok presented hopeful findings in melanoma at the ASCO Plenary Session. Photo courtesy of ASCO.

Studies continue to demonstrate the success of immunotherapy, a type of treatment that boosts the immune system’s inherent ability to defend against cancer. Memorial Sloan Kettering researchers have played an important role in the development of nivolumab and ipilimumab, drugs that unleash immune cells called T cells to more readily seek out and destroy tumors.

An international clinical trial in patients with advanced melanoma that assesses the effectiveness of these drugs — known as immune checkpoint blockade therapies — used either on their own or together is the latest in a recent wave of major breakthroughs. The early results of the study, the first side-by-side comparison of the two drugs, show that nivolumab on its own is more effective than ipilimumab alone. It also validates findings from a smaller recent study in which MSK researchers found that administering the two drugs in conjunction produces significantly better outcomes than giving ipilimumab on its own. (It didn’t compare the combination with nivolumab alone.)

In addition, the findings suggest a possible way to determine whether individual patients are likely to benefit from the drug combination, based on the biology of their tumors.

MSK medical oncologist and immunotherapy expert Jedd Wolchok presented the new findings in yesterday’s plenary session of the annual meeting of the American Society of Clinical Oncology — which is taking place in Chicago — to a rapt audience of cancer doctors and researchers. The results from the ongoing phase III clinical trial, which involves close to a thousand patients from around the world, were also published on the same day in the New England Journal of Medicine.

We sat down with Dr. Wolchok to talk about the new findings and their implications.

Tell us about the study and its main findings.

The trial enrolled 945 patients with advanced melanoma who hadn’t received immunotherapy or any other cancer treatment previously. The patients were randomly divided into three groups: one group receiving injections of nivolumab plus ipilimumab, another receiving nivolumab injections with a placebo, and a third group receiving ipilimumab and a placebo.

Compassionate Use

An expanded access program will allow some patients to receive the drug combination ahead of FDA approval.

After following the patients for nine months, we found that those receiving nivolumab alone lived more than twice as long without their disease progressing compared with those treated with ipilimumab alone. On average, the length of progression-free survival was about seven months in the nivolumab group and three months in the ipilimumab group.

Importantly, we saw the strongest effectiveness of the drugs among patients receiving both therapies together. In this group, people lived without disease progression for 11.5 months on average. Although we still don’t have data about overall survival — the extent to which the drug combination prolongs patients’ lives — these preliminary findings are very exciting and hopeful.

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Are these findings of immediate value for people with advanced melanoma?

Yes, we expect this will expand treatment options for patients with the disease. Here at MSK, we’ve opened an expanded access program that allows patients who are not involved in the ongoing clinical trial to receive the drug combination. Expanded access, or “compassionate use,” is a way in which the US Food and Drug Administration makes it possible for patients with a serious disease to gain access to potentially lifesaving drugs or drug combinations before they become commercially available.

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Is it always better for melanoma patients to receive the two drugs in combination?

These preliminary findings are very exciting and hopeful.
Jedd D. Wolchok Chief, Melanoma and Immunotherapeutics Service; Lloyd J. Old Chair for Clinical Investigation

Not necessarily. In fact, our study suggests that some melanoma patients may get the same benefit from taking nivolumab on its own as they would from taking the drug combination. These are people whose tumors make a protein called PD-L1, which is part of an immune-regulating process that nivolumab blocks. (Ipilimumab, on the other hand, blocks a different immune regulating process by targeting the protein CTLA-4.)

In the study, we monitored PD-L1 expression in patients’ tumors by pathology testing. Among patients whose tumors express PD-L1, those receiving nivolumab alone remained disease-free for as long as those taking both nivolumab and ipilimumab — 14 months on average. On the other hand, the likelihood of a patient having a significant decrease in tumor size was higher with the combination than with nivolumab, regardless of the extent of PD-L1 expression.

Another important finding is that people who received both drugs reported more-severe side effects — including colitis, or inflammation of the colon, which in rare cases can be dangerous — compared with those receiving either drug on its own. So in deciding about treatment, doctors and patients will need to take into account the risk of side effects as well as the potential benefit of receiving a drug combination. For example, if a patient’s melanoma is PD-L1 negative and side effects can be managed, it might make sense to offer the combination therapy.

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The results from the phase I clinical trial of this drug combination were presented at the 2013 ASCO meeting. What accounts for the fast pace of progress?

It’s indeed remarkable that we’ve gone from phase I to phase III [the early and late stages of clinical testing, respectively] in less than two years. This is due to the powerful effects these drugs produce. For some melanoma patients, aggressive tumors have been shown to virtually melt away.

More importantly, as we present the new data, we pause and thank the patients who enrolled in these trials — indeed, in any clinical trial. These individuals are blazing the trails of cancer research, and we are indebted to them for helping to better the care of patients in generations to come.

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Has the ipilimumab-nivolumab combination been tested in any other types of cancer?

At MSK, we are currently testing single and combination immunotherapies in a range of advanced cancers — including kidney cancer, lymphoma, breast cancer, gastric cancer, pancreatic cancer, small cell lung cancer, and bladder cancer — hoping that the added benefit of combining the drugs is not unique to melanoma. For most of these diseases, the trials are still in their early stages.

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This research was sponsored by Bristol-Myers Squibb.


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Dear Morris, according to the study mentioned in the blog post, doctors followed the patients for nine months and found that those receiving nivolumab alone lived more than twice as long without their disease progressing compared with those treated with ipilimumab alone. However, they saw the strongest effectiveness of the drugs among patients receiving both therapies together. In this group, people lived without disease progression for 11.5 months on average.

It’s important to note that these are averages that don’t necessarily apply to every patient, since everyone responds to these drugs differently. We see often see people do better than expected. To learn more about treatment for people with advanced melanoma, please visit

If you would like to make an appointment for a consultation with one of our specialists to discuss your treatment options, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.