FDA Approves Opdivo, Yervoy Combination for Mesothelioma

The U.S. Food and Drug Administration has approved the immunotherapy combination of Opdivo and Yervoy for first-line treatment of unresectable malignant pleural mesothelioma.

It was the first new drug regimen approved for mesothelioma in 16 years and only the second systemic therapy ever.

The historic treatment approval for this cancer without a cure was the first since the FDA approved the chemotherapy combination of pemetrexed and cisplatin in 2004.

“This marks the beginning of a new era for mesothelioma,” Dr. Bernardo Goulart, medical oncologist at Seattle Cancer Care Alliance, told The Mesothelioma Center at Asbestos.com. “This is remarkable. A huge step. I’d say a historic landmark. The progress in treating this disease has been so slow.”

Approval was granted on Oct. 2 to pharmaceutical company Bristol Myers Squibb, which manufactures Opdivo and Yervoy, known generically as nivolumab and ipilimumab, respectively.

The FDA previously approved the combination for first-line treatment of metastatic non-small cell lung cancers with certain characteristics. It is the only other thoracic cancer for which it is approved.

“This combination is a game changer, showing unquestionable survival benefits for mesothelioma,” Goulart said. “It confirms the disease is subject to the harnessing of the immune system. This will open a lot of doors.”

In 2019, the FDA did approve the use of NovoTTF-100L, known as Tumor Treating Fields, under the agency’s Humanitarian Device Exemption. The therapy involves alternating electrical fields and is designed for continual use for up to 18 hours a day.

Until now, the most effective therapy for pleural mesothelioma has been a multidisciplinary combination of chemotherapy, surgery and radiation.

Aggressive mesothelioma surgery, though, is used in less than one-third of those diagnosed. Surgery is typically not an option because the disease is too advanced at the time of diagnosis.

Immunotherapy Trial Shows Survival Advantage

The approval comes in the wake of a multicenter, international phase III clinical trial in which the combination demonstrated superior overall survival when compared to chemotherapy alone. The name of the trial, sponsored by Bristol Myers Squibb, was CheckMate 743.

Patients who were treated with the Opdivo and Yervoy immunotherapy combination had a median overall survival of 18.1 months, compared with 14.1 months for those receiving chemotherapy alone.

The two-year survival rate was 41% for those receiving the immunotherapy combination, but only 27% for the chemotherapy group.

Although the survival improvement was modest overall, it was dramatic in the traditionally toughest-to-treat subtypes of mesothelioma.

For patients with sarcomatoid or biphasic mesothelioma (non-epithelioid histology), the median survival was just 8.8 months for those receiving chemotherapy. It was 18.1 months for those getting the immunotherapy.

The two-year survival rate jumped from 8% to 38% for the same two categories. The results were presented at the World Conference on Lung Cancer virtual meeting earlier this year.

“Overall, the difference was not huge, but what I thought was hopeful were the results with those toughest-to-treat patients,” Dr. Raja Flores, thoracic surgeon at Mount Sinai Hospital in New York City, told The Mesothelioma Center and Asbestos.com. “If those results hold true, then finally we have made a breakthrough in this subtype.”

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Combination Immunotherapy Is Key to Mesothelioma Treatment

Although dozens of immunotherapy drugs today are being studied on mesothelioma tumors, experts agree that finding the right combination will be the key to improving treatment.

Opdivo and Yervoy have proven to be unique together. Both are known as checkpoint inhibitors, but they work in different ways. With mesothelioma, they develop an effective synergistic mechanism with T cells, a type of white blood cell and part of the immune system.

Opdivo helps the T cells discover the tumor, while Yervoy proliferates and activates the T cells.

“This is exciting news, instilling hope for patients with this devastating disease and for health care providers who care for them,” Dr. Anne Tsao, director of the mesothelioma program at MD Anderson Cancer Center in Houston, said in a press release from Bristol Myers Squibb.

The randomized trial involved more than 600 patients across 114 different treatment centers, including 14 within the U.S. Half the patients received the immunotherapy combination.

And while the immunotherapy combination showed a definitive survival advantage, it revealed some adverse side effects.

Treatment was discontinued by 23% of the patients because of adverse reactions and 52% had at least one dose withheld because of a reaction.

The FDA approval involves receiving Opdivo every three weeks and Yervoy every six weeks.

“By no means is it a walk in the park in terms of side effects,” Goulart said. “Patients need to be aware of that. However, I believe this is history for mesothelioma. Clinical pathways will be modified because of what happened today.”

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