The FDA has now approved nivolumab (Opdivo®, Bristol Myers Squibb) in combination with ipilimumab (Yervoy®, Bristol-Myers Squibb) as first-line treatment for unresectable malignant pleural mesothelioma (MPM). This therapeutic combination is only the second treatment to be FDA approved for this condition, and it marks the first mesothelioma approval to take place in the past 16 years.
The approval was based on efficacy data from the open-label phase 3 CHECKMATE 743 trial (NCT02899299), for which 605 patients with treatment-naive, unresectable MPM were randomized in a 1:1 ratio to receive either nivolumab/ipilimumab for up to two years or combination chemotherapy, consisting of pemetrexed and cisplatin or carboplatin, for six cycles. Nivolumab/ipilimumab significantly increased median overall survival compared with chemotherapy (18.1 vs 14.1 months), even though it did not prolong progression-free survival (6.8 months for nivolumab/ipilimumab vs 7.2 months for chemotherapy, a difference which was not statistically significant). Confirmed overall response rate per blinded independent central review was 40% for nivolumab/ipilimumab, compared with 43% for chemotherapy. Nivolumab/ipilimumab produced a longer median response duration (11.0 vs 6.7 months).
"Today's approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma," commented Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, in a press release. "Now patients now have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen."
Adverse reactions affecting at least 20% of patients taking nivolumab/ipilimumab in the trial included fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus. Ipilimumab is known to cause immune-mediated adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
For patients with MPM, the recommended dosages are nivolumab 360 mg every three weeks and ipilimumab 1 mg/kg every six weeks until disease progression or unacceptable toxicity, or for up to two years in patients without disease progression.
For More Information
Clinicaltrials.gov (2020). Study of nivolumab combined with ipilimumab versus pemetrexed and cisplatin or carboplatin as first line therapy in unresectable pleural mesothelioma patients (CheckMate743). NLM identifier: NCT02899299.
US Food & Drug Administration (2020). FDA approves nivolumab and ipilimumab for unresectable malignant pleural mesothelioma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-and-ipilimumab-unresectable-malignant-pleural-mesothelioma
Yervoy® (ipilimumab) prescribing information (2020). Bristol Myers Squibb. Available at: https://packageinserts.bms.com/pi/pi_yervoy.pdf
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