The Food and Drug Administration (FDA) has approved Opdivo® (nivolumab; Bristol Myers Squibb) plus Yervoy® (ipilimumab; Bristol Myers Squibb) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma.
The approval was based on a pre-specified interim analysis from the open-label phase 3 CheckMate -743 trial. The study evaluated the effectiveness and tolerability of nivolumab, a programmed death receptor-1 blocking antibody, plus ipilimumab, a human cytotoxic T-lymphocyte antigen 4-blocking antibody, in 605 patients with histologically confirmed and previously untreated malignant pleural mesothelioma with no palliative radiotherapy within 14 days of initiation of therapy. Patients were randomized 1:1 to receive nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=303), or platinum-based standard of care chemotherapy (pemetrexed plus cisplatin or carboplatin) in 3-week cycles for 6 cycles (n=302). The primary end point was overall survival (OS).
At the time of analysis, results showed a statistically significant improvement in OS with nivolumab plus ipilimumab compared with chemotherapy (median OS of 18.1 months [95% CI, 16.8-21.5] vs 14.1 months [95% CI, 12.5-16.2], respectively; hazard ratio [HR] 0.74; 95% CI, 0.61-0.89; P =.002).
“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,” 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 the subgroup of patients with epithelioid histology, the HR for OS was 0.85 (95% CI, 0.68-1.06), with a median OS of 18.7 months in the nivolumab plus ipilimumab group vs 16.2 months in the chemotherapy group. Among patients with non-epithelioid histology, the HR for OS was 0.46 (95% CI, 0.31-0.70); the median OS was 16.9 months and 8.8 months in the nivolumab plus ipilimumab and chemotherapy arms, respectively.
As for safety, the most common adverse reactions reported with nivolumab plus ipilimumab in patients with malignant pleural mesothelioma were fatigue, musculoskeletal pain, rash, dyspnea, nausea, decreased appetite, cough and pruritus.
“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,” said 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 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients now have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen.”
The combination of Opdivo and Yervoy has been approved for several indications including: unresectable or metastatic melanoma; intermediate or poor risk, previously untreated advanced renal cell carcinoma; microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer; non-small cell lung cancer; and hepatocellular carcinoma in patients previously treated with sorafenib.
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- U.S. Food and Drug Administration approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) as the first and only immunotherapy treatment for previously untreated unresectable malignant pleural mesothelioma. https://www.businesswire.com/news/home/20201002005481/en/U.S.-Food-and-Drug-Administration-Approves-Opdivo%C2%AE-nivolumab-Yervoy%C2%AE-ipilimumab-as-the-First-and-Only-Immunotherapy-Treatment-for-Previously-Untreated-Unresectable-Malignant-Pleural-Mesothelioma. Accessed October 5, 2020.
- FDA approves drug combination for treating mesothelioma. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-combination-treating-mesothelioma. Accessed October 5, 2020.