Nick Mulcahy

May 19, 2016

CHICAGO — Which anti-PD-1 immunotherapy should you choose for the treatment of advanced melanoma: nivolumab (Opdivo, Bristol-Myers Squibb) or pembrolizumab (Keytruda, Merck)?

In a refreshing display of academic impartiality, pembrolizumab investigator Caroline Robert, MD, PhD, from the Institut Gustave-Roussy in Paris, said it doesn't much matter.

"Honestly, I don't see any difference," she said when asked which drug is superior in terms of efficacy and safety at a presscast held in advance of the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

Dr Robert's candor was trumped by scientific rigor from presscast host and ASCO President Julie Vose, MD, MBA, who is from the University of Nebraska in Omaha.

"To answer that question, we would really need a large phase 3 randomized trial," said Dr Vose.

But Dr Robert was not finished being candid.

That would not be very exciting.

"That would not be very exciting," she countered, "because we have so many exciting things to evaluate." For example, she said, there is a need for studies combining these new immunotherapies with existing and emerging melanoma treatments.

Dr Vose agreed. "Right," she said.

During the presscast, Dr Roberts discussed new 3-year survival data for patients with advanced melanoma treated with pembrolizumab, which will be presented in full at the meeting.

The data come from the phase 1b KEYNOTE-001 trial of 655 patients with newly diagnosed or previously treated advanced melanoma who received single-agent pembrolizumab. Early results from this trial led to accelerated approval of the drug in September 2014.

Now, Dr Robert reported more mature survival data. Three years after starting on pembrolizumab, 41% of patients are still alive, and 36-month overall survival rates are similar in newly diagnosed and previously treated patients.

Durable responses were seen in 33% of the study participants. Of these responders, 73% had a response duration of at least 2 years.

Complete responses were seen in 15% of the study cohort (95 patients). Of these, 61 patients stopped pembrolizumab after a complete response was achieved (median treatment duration, 23 months). And only two of these patients have since progressed (one resumed therapy); the other 59 were still in remission at the time of analysis.

I really hope for a cure for these patients.

"I really hope for a cure for these patients," Dr Robert said.

Another expert also used the C word.

"It is incredibly encouraging that we could potentially see a cure in melanoma," said presscast moderator Don Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, citing as evidence the high percentage of responders who have had long responses.

The results are especially "exciting" because they come from a phase 1 trial, he added.

In recent years, various experts have ventured to use "cure" or "breakthrough" in the context of maturing results from early-phase immunotherapy trials in advanced melanoma.

The Same and No Difference

The new survival data for pembrolizumab are similar to those recently reported for nivolumab. Last month at the annual meeting of the American Cancer Research Association, nivolumab investigators reported that 34% of patients with advanced melanoma who received the immunotherapy in a 107-patient phase 1 clinical trial were still alive 5 years after starting treatment, as reported by Medscape Medical News.

The survival percentages for the two drugs are "close," said Ashani T. Weeraratna, PhD, a melanoma researcher at The Wistar Institute in Philadelphia, who was asked for comment.

Dr Roberts pointed out that the overall response rates for the two melanoma therapies are "the same," and that roughly the same percentage of treated patients were alive at 1 and 2 years.

The adverse events are also "very similar" between the two treatments, with about 15% of patients experiencing events of grade 3 or higher. "I don't see any difference," she noted.

"There is a long benefit with nivolumab and a long benefit with pembrolizumab," said Dr Robert. "It's exactly the same."

There is a minor difference in the administration of the two drugs: nivolumab is administered every 2 weeks and pembrolizumab every 3 weeks.

Patients who want to be followed more closely might prefer every 2 weeks and those who prefer less-intensive follow-up might prefer 3 weeks, said Dr Roberts.

Eventually, the price of the drug could prove to be a big differentiator and the basis upon which clinicians and health systems chose one drug over the other, she added.

In any event, the treatment of advanced melanoma has undergone rapid and great change, suggested Dr Robert. Since the 2011 approval of ipilimumab, the first immunotherapy for melanoma, "things have changed a lot," she said.

Before that time, patients with advanced melanoma had a median overall survival of less than 1 year.

Pembrolizumab is also approved for lung cancer and nivolumab is also approved for renal cell carcinoma, lung cancer, and Hodgkin's lymphoma. But the most impressive results to date for both drugs have been in melanoma.

This is because "melanoma is a particularly immunogenic cancer, in part because the proteins that make melanin, the pigment in these cells, also act as antigens, or essentially 'red flags' for the immune cells," Dr Weeraratna told Medscape Medical News. "Unfortunately, this is not true for all solid tumors."

This study received funding and support from Merck. Dr Robert reports serving in a consulting or advisory role for Bristol-Myers Squibb, Roche, Merck, Amgen, Novartis, and GlaxoSmithKline. Dr Dizon reports financial relationships with UptoDate and Aeterna Zentaris. Dr Vose has disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract 9503. To be presented June 6, 2016.

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