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Expert Point of View: Marc S. Ernstoff, MD


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What we did not learn from these trials is whether ipilimumab is of benefit after failure on pembrolizumab or nivolumab.
— Marc S. Ernstoff, MD

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The field of studies of combination immunotherapies is exploding, and “the future looks bright, with currently 71 trials of combination therapy in melanoma,” said formal discussant of these trials Marc S. Ernstoff, MD, of Roswell Park Cancer Institute, Buffalo, New York.

“We now know that anti–PD-1 (programmed cell death protein 1) therapy is preferred as first-line therapy in advanced melanoma. Pembrolizumab (Keytruda) and nivolumab (Opdivo) have not been studied head to head as single-agent therapy. There is probably no difference between these agents as single-agent therapy. Outcomes with both agents are consistently similar in advanced melanoma,” he shared.

“Dr. Wolchok said that response to the combination therapy will be ongoing, and my suspicion is that we will continue to see improvement in that arm,” Dr. Ernstoff noted. “There is a high percentage of low-grade toxicities on combination therapy, and as patients survival longer, these will become more important for quality of life,” he added.

Issues Remain

“What we did not learn from these trials is whether ipilimumab (Yervoy) is of benefit after failure on pembrolizumab or nivolumab. Also we didn’t learn whether to continue treatment past disease progression. What is the optimal number of doses of ipilimumab?” continued Dr. Ernstoff.

Also, cost is an issue. The cost of immunotherapy is about $100,000 per year per patient. “We will have to address cost,” he acknowledged.

Dr. Ernstoff urged oncologists to enroll patients on ECOG (Eastern Cooperative Oncology Group) 6134, a study that is evaluating the optimal sequencing of immune checkpoint and targeted therapies.

Disclosure: Dr. Ernstoff reported no potential conflicts of interest.


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Nivolumab plus ipilimumab continue to demonstrate superior clinical activity vs ipilimumab monotherapy, with greater efficacy than with either drug alone, regardless of PD-L1 expression or BRAF mutation status.
— Jedd Wolchok, MD, PhD

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