FDA’s Approval of Opdivo-Yervoy for Unresectable Malignant Pleural Mesothelioma was ‘Desperately Needed’, But Questions Remain

The Food and Drug Administration’s (FDA) recent approval of Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the frontline treatment of adults with unresectable malignant pleural mesothelioma was desperately needed, according to Dr. Marjorie G. Zauderer.

“I was really excited when I heard the news,” said Zauderer, a thoracic medical oncologist and co-director of the Mesothelioma Program at Memorial Sloan Kettering Cancer Center, in an interview with CURE®. “There hasn't been a new regimen approved for mesothelioma in over 15 years. And it's always great to have more options to consider for patients.”

The approval was based on results of the multi-center, open-label phase 3 CheckMate-743 trial, which showed that the Opdivo-Yervoy combination induced a superior overall survival (OS) in patients compared with platinum-based standard-of-care chemotherapy.

After a median follow-up of 22.1 months, participants who received the combination (303 patients) achieved a median OS of 18.1 months compared to 14.1 months in those who received the standard-of-care chemotherapy (302 patients).

Of note, 41% of patients treated with Opdivo and Yervoy were alive at two years compared to 27% treated with the chemotherapy regimen.

“This was really desperately needed. So many patients go through regular treatment, and it works for a while or it doesn't work, and they need other options,” said Zauderer. “And to have another option, particularly up front when people are at their healthiest and best able to tolerate treatment is great. We've seen immunotherapy really come into primetime for lots of other malignancies and it's nice to see it come forward for a less common disease like mesothelioma.”

Typically, Zauderer noted, oncologists spend a significant amount of time reviewing surgery as part of a patient’s treatment plan, which is important for those who have early-stage disease, but not everyone is a candidate for surgery. In fact, most patients diagnosed with mesothelioma can’t receive a resection mostly because of the distribution of the disease in the chest.

“Their initial treatment is systemic therapy,” she said. “And that really becomes the backbone of whatever treatment plan you develop.”

Devil in the Details

Zauderer said that the “devil is in the details” when it comes to assessing how the combination of Opdivo and Yervoy compares to other traditional therapies that have been used to treat this disease.

She noted that the data that led to the approval of the combination indicated that it fared better than the combination of the chemotherapies cisplatin and Alimta (pemetrexed) in two subtypes of mesothelioma – sarcomatoid and biphasic.

However, Zauderer said, the difference between the Opdivo-Yervoy combination and chemotherapy was much smaller in patients with epithelioid mesothelioma, which is the most common subtype of the disease.

“So, I think that in terms of how we implement this option into our practice, there’s still some questions,” she said.

Of note, according to Zauderer, patients with epithelioid disease often will receive three chemotherapy agents as treatment, but the trial that led to the approval only included two chemotherapies.

“When you factor in that the difference is smaller and it’s only compared to two drugs, well, is three chemo drugs better than ipilimumab and nivolumab,” she questioned. “But certainly, it’s a highly effective way of treating patients. And, it spares them the toxicities of chemotherapy.”

And although patients would be spared from the toxicities associated with chemotherapy, Zauderer stressed that patients who receive immunotherapy still can face side effects as well.

More Work is Needed

When reviewing the data, Zauderer said, it’s clear that some people derived an overall survival benefit from the Opdivo and Yervoy combination. However, the results of the trial didn’t show that progression free survival early on was any better in those who received the combination immunotherapy versus the combination chemotherapy.

“As an oncologist, when I think about the individuals that I'm treating, I always worry about a person having that sort of rapid progression,” she concluded. “And what we really need as a community are better biomarkers to tell us this is a person who's really likely to respond. This is a person who might respond but it might take a while versus someone who isn't and then that will really help us parse out who should get which treatment and help us really personalize those decisions.”

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