麻豆传媒

The FDA on Friday approved dual checkpoint blockade with nivolumab (Opdivo) plus ipilimumab (Yervoy) for the .

Support for the approval was based on findings from CheckMate 743, an open-label phase III trial that randomized 605 patients with unresectable malignant pleural mesothelioma to either standard platinum-based chemotherapy or the PD-1 inhibitor nivolumab (360 mg every 3 weeks) in combination with the anti-CTLA-4 drug ipilimumab (1 mg/kg every 6 weeks).

"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 investigator Anne Tsao, MD, of MD Anderson Cancer Center in Houston, in a from drugmaker Bristol-Myers Squibb. "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."

Median overall survival in the study reached 18.1 months with nivolumab-ipilimumab, as compared to 14.1 months with chemotherapy (HR 0.74, 95% CI 0.61-0.89, P=0.002), and survival rates at 2 years were 41% versus 27%, respectively.

"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," Richard Pazdur, MD, the top hematology/oncology official at the FDA, said in a statement. "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."

Common adverse events (AEs) with the immunotherapy combination (at least 20%) included fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus. Treatment discontinuation due to toxicity occurred in 23%, and about half had dose interruptions. Additionally, 4.7% of patients discontinued ipilimumab alone due to toxicity.

Serious AEs occurred in a little more than half, the most frequent (≥2%) of which were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Four patients died due to treatment-related AEs.

Friday's approval marks the third for nivolumab-ipilimumab as an initial treatment in thoracic cancers, following two recent approvals for metastatic non-small cell lung cancer -- in combination with two cycles of chemotherapy for all adult patients, or as a chemotherapy-free option for those expressing PD-L1 (≥1%).

The combination is also approved for the treatment of advanced melanoma, renal cell carcinoma, liver cancer, and for colorectal cancer patients with microsatellite instability-high or mismatch repair-deficient tumors.

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