FDA Approves Nivolumab Plus Ipilimumab for Malignant Pleural Mesothelioma

The FDA approved nivolumab (Opdivo) plus ipilimumab (Yervoy) for the frontline treatment of adults with unresectable, malignant, pleural mesothelioma (MPM), according to Bristol Myers Squibb, the manufacturer of the immunotherapy agents.

“Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the five-year survival rate is approximately 10 percent,” said study investigator Anne S. Tsao, MD, professor and Section Chief Thoracic Medical Oncology and Director of the Mesothelioma Program at The University of Texas M.D. Anderson Cancer Center, in a statement.

The approval, which is for 360 mg of nivolumab every 3 weeks, plus 1 mg/kg every 6 weeks via IV of ipilimumab, was based on an interim analysis of the open-label, multi-center, randomized, phase III CheckMate-743 trial, which showed a median overall survival (OS) rate of 18.1 months for the combination, compared to 14.1 months for platinum-based standard of care (pemetrexed and cisplatin or carboplatin) at 22.1 months of minimum follow-up.

While OS was the primary outcome of CheckMate-743, additional outcome measures were progression-free survival, objective response rate, and duration of response, as assessed by BICR using modified RECIST criteria.

At the 2-year mark, 41% of patients treated with nivolumab plus ipilimumab were alive, compared with 27% of those on the chemotherapy regimen.

Treatment with nivolumab and ipilimumab — both checkpoint inhibitors – can come with immune-mediated adverse events (AEs) that nurses should look out for, including: colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis.

Additional AEs include infusion reactions; complications of stem-cell transplant that uses donor stem cells (allogeneic); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when nivolumab is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

“Thoracic cancers can be complex and difficult to treat, and we are focused on developing immunotherapy options that may have the potential to extend patients’ lives,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb.

“Now, [ipilimumab plus nivolumab] is approved for use in another type of thoracic cancer, previously untreated unresectable MPM. With today’s announcement, [ipilimumab plus nivolumab] becomes the first new systemic therapy approved in more than 15 years in this setting, and may offer these patients a chance for a longer life.”

MPM is the most common type of mesothelioma, which is a rare yet aggressive form of cancer that often occurs in the lining of the lungs. It often is caused by exposure to asbestos, and since the diagnosis can be elusive, patients are often diagnosed at later stages with poor prognoses.

“The survival results from the CheckMate-743 trial show that the combination of nivolumab and ipilimumab could become a new front-line standard of care option. This is exciting news, instilling hope for patients with this devastating disease and for the healthcare providers who care for them,” Tsao said.