Nivolumab–Ipilimumab Immunotherapy Combination Receives FDA Approval for Malignant Mesothelioma

Nivolumab (Opdivo) plus ipilimumab (Yervoy), a combination of two immunotherapy drugs, received approval for unresectable malignant pleural (lung lining) mesothelioma in adult patients as first-line treatment on October 2, 2020, from the US Food and Drug Administration (FDA). This is the first FDA immunotherapy approval for mesothelioma. We thus gained an approved chemotherapy-free treatment option for mesothelioma regardless of subtype.

The efficacy of nivolumab plus ipilimumab was investigated in a randomized, open-label trial of patients with inoperable malignant pleural mesothelioma who had not previously received cancer treatment, CHECKMATE-743.

Related topic: What Is Mesothelioma? A Detailed Commentary on the CHECKMATE-743 Study

The CHECKMATE-743 Study in Brief

• Patients were randomized to 2 arms to receive nivolumab and ipilimumab for up to 2 years (303 patients), or 6 cycles of combination chemotherapy with the standard treatment, cisplatin or carboplatin plus pemetrexed (302 patients).
• The study found that patients treated with nivolumab plus ipilimumab had better median overall survival than those receiving chemotherapy: 18.1 months versus 14.1 months.
• Median progression-free survival (PFS) was 7.2 months in the nivolumab plus ipilimumab arm versus 6.8 months in the chemotherapy arm.
• Median response duration was 11 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm.

The CHECKMATE-743 study's graphical summary is provided below:

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• In CHECKMATE-743, the most common (frequency ≥% 20) adverse effects in patients receiving nivolumab plus ipilimumab were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough and itching.
• The recommended dose of nivolumab plus ipilimumab for malignant pleural mesothelioma, until disease progression or unacceptable adverse effects, is 360 mg of nivolumab every 3 weeks and 1 mg / kg of ipilimumab every 6 weeks or for up to 2 years in patients without disease progression.

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What Is Pleural Mesothelioma?

Our lungs are covered by a two-layer membrane called the pleura. A small amount of fluid lies between the pleural layers and is produced by mesothelial cells. Tissues similar in structure to the lung's pleural membrane are also found elsewhere in the body. They are called the peritoneum around the abdomen and the pericardium around the heart. Malignant mesothelioma is the name of cancer arising from these membranes. Malignant mesothelioma originating in the pleural membrane accounts for 80% of patients with malignant mesothelioma.

What Causes It? The most important cause of malignant mesothelioma is asbestos exposure. More rarely, genetic causes and a virus called Simian 40 cause it.

Mesothelioma, a rare cancer, is more common in men in countries with occupational asbestos exposure, while rates in women and men are equal where exposure is environmental, as in Turkey. Worldwide incidence is 1-2 per 1 million people, while around 500 people receive a new mesothelioma diagnosis annually in Turkey.

The Latest Developments in Pleural Mesothelioma Treatment

With this approval, there are 3 FDA-approved treatments for pleural mesothelioma: "cisplatin + pemetrexed" chemotherapy, the addition of electrical current therapy (NovoTTF-100L System) to this chemotherapy, and the nivolumab–ipilimumab combination. In addition, the cisplatin + pemetrexed doublet can be supplemented with bevacizumab (Altuzan, Avastin, Mvasi), a drug that inhibits new blood vessel formation, an antiangiogenic agent. We know from the phase-III trial whose results were announced in 2015, MAPS, that this addition significantly improves survival rates, and we try to incorporate it into treatment in clinical practice by applying for Off-Label Authorization. The CheckMate 743 study discussed here, with the best results to date particularly in the non-epithelioid subtype, also showed that  combination immunotherapy is effective in treating mesothelioma and that chemotherapy-free treatment may be possible, leading to FDA approval of combination immunotherapy for first-line pleural mesothelioma treatment.

Below, you can see the FDA-approved treatments for pleural mesothelioma and their indirect comparison:

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