The U.S. Food and Drug Administration (FDA) has approved the immunotherapy pembrolizumab (Keytruda) in combination with chemotherapy as an initial treatment for adults with metastatic malignant pleural mesothelioma.
The news is a game-changer for the treatment of mesothelioma and offers new hope to patients who have run out of options.
Pembrolizumab’s Role in Mesothelioma Treatment
Results of the pivotal, open-label phase three KEYNOTE-483 trial evaluating first-line pemetrexed and platinum-based chemotherapy with pembrolizumab for patients with advanced mesothelioma also supported the FDA approval.
Despite the fact this trial displayed OS and PFS benefits compared with chemotherapy alone, it was found to be somewhat counterintuitive since new drug notching mechanisms were highly targeted at the EGFR pathway.
Pembrolizumab is among a class of drugs called immune checkpoint inhibitors, designed to work by blocking the PD-1 pathway that some mesothelioma cancer cells use to avoid detection by the immune system.
Pembrolizumab blocks this pathway, which prevents the immune system from recognizing and killing cancer cells. If mesothelioma is not resectable, this regimen has worked well with other cancers, making the approval for mesothelioma an even greater help to patients who have inoperable forms of the disease.
Key Trial Results: Improved Survival and Response Rates
The KEYNOTE-483 study was performed in patients with previously untreated, advanced malignant pleural mesothelioma. Key findings included:
Better OS: Median OS of 17.3 months in the pembrolizumab plus chemotherapy group versus 16.1 with chemotherapy alone;
Longer PFS: Pembrolizumab was more effective at holding cancer at bay, delaying disease progression longer than chemotherapy alone.
Greater Overall Response Rate (ORR): A statistically greater percentage of initial responses occurred in the pembrolizumab arm.
Safety Considerations and Side Effects
Side effects of the combination of pembrolizumab and chemotherapy include fatigue, nausea, anemia, decreased appetite, and diarrhea. A rare risk, but a real one is an immune-mediated side effect particularly pneumonitis, hepatitis, or colitis which are more serious so it should be carefully monitored. But sometimes, especially with a disease like mesothelioma, the benefits may exceed the risks related to pembrolizumab.
The FDA’s approval of pembrolizumab for advanced mesothelioma was facilitated through Project Orbis, an international initiative aimed at accelerating access to innovative cancer therapies.
