FDA Approves Nivolumab and Ipilimumab for Malignant Pleural Mesothelioma
On October 2, 2020, the U.S. Food and Drug Administration (FDA) approved (http://fda.gov/news-events/press-announcements/fda-approves-drug-combination-treating-mesothelioma?utm_medium=email&utm_source=govdelivery) nivolumab (Opdivo®) in combination with ipilimumab (Yervoy®) for the first-line treatment of adults with malignant pleural mesothelioma (MPM) that cannot be removed by surgery. This is the first drug regimen approved for mesothelioma in 16 years and the second FDA-approved systemic therapy for mesothelioma.
Nivolumab and ipilimumab are both monoclonal antibodies that, when combined, decrease tumor growth by enhancing T-cell function.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with MPM,” Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence (OCE) and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, said. “In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen.”
The combination therapy was evaluated during a randomized, open-label trial of 605 patients with previously untreated unresectable MPM. Patients received IV infusions of nivolumab every two weeks with IV infusions of ipilimumab every six weeks for up to two years or platinum-doublet chemotherapy for up to six cycles.
Treatment continued until patients experienced disease progression, unacceptable toxicity, or completed two years of therapy. The objective was to determine whether nivolumab in combination with ipilimumab improved overall survival compared to chemotherapy. At the time of the analysis, patients who received nivolumab in combination with ipilimumab survived a median of 18.1 months whereas patients who underwent chemotherapy survived a median of 14.1 months.
The most common side effects of nivolumab in combination with ipilimumab in patients with MPM are fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritis. Ipilimumab can cause immune-related adverse events, including
colitis, hepatitis, dermatologic adverse reactions, endocrinopathies, pneumonitis, and nephritis with renal dysfunction, which can occur at any time during treatment or after discontinuation.
View full prescribing information for nivolumab (https://packageinserts.bms.com/pi/pi_opdivo.pdf).
View full prescribing information for ipilimumab (https://packageinserts.bms.com/pi/pi_yervoy.pdf).
The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of FDA’s OCE. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. FDA approval occurred approximately five months ahead of the goal date.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).