Update (09/18/2024): In September 2024, the FDA approved Keytruda as a first-line treatment for unresectable, malignant pleural mesothelioma.
After 15 years without approving any new therapies for mesothelioma, the U.S. Food and Drug Administration approved two in consecutive years.
The FDA green-lit a tumor treating fields device in 2019 and an immunotherapy regimen in 2020.
So the question now is, “What’s next?”
The FDA first approved the NovoTTF-100L System, now called Optune Lua. The tumor treating fields device was the first approval since the FDA approved the chemotherapy drugs cisplatin and pemetrexed.
The FDA most recently approved Opdivo and Yervoy, two immunotherapy drugs used together for malignant mesothelioma.
Three new therapies appear close to FDA approval for mesothelioma. Each could be approved for similar cases as the last two: unresectable malignant mesothelioma (ineligible for surgery).
ONCOS-102
ONCOS-102 is an oncolytic adenovirus that stimulates an immune response to mesothelioma. In other words, it’s a virotherapy that transitions into an immunotherapy.
ONCOS-102 delivers a virus into the tumor microenvironment. The virus breaks apart mesothelioma cells, which release hidden antigens. These antigens alert the immune system, which then attacks the tumor.
The FDA already favors ONCOS-102. The agency granted “fast-track designation” to the therapy, allowing for an accelerated review and approval process. ONCOS-102 has shown better survival results and fewer side effects compared to chemotherapy.
The FDA recognizes the lack of therapeutic options for mesothelioma, particularly for patients whose cancer is too advanced for surgery. The fast-track designation highlights ONCOS-102’s potential to fill that gap.
Keytruda
The FDA has already granted limited approval for Keytruda (pembrolizumab). Currently, the drug can only be used in cases with high expression of the PD-1/PD-L1 protein connection, which suppresses the immune system.
With the approval of Opdivo — another PD-1/PD-L1 checkpoint inhibitor — there are now two immunotherapy options for this subset of patients. The next step for Keytruda is broader approval, potentially for all unresectable malignant mesothelioma cases.
The PROMISE study produced discouraging survival results, as Keytruda did not outperform chemotherapy. However, many experts remain optimistic and continue exploring its potential.
The most promising approach appears to be combining Keytruda with chemotherapy, surgery, or radiation. For example, a trial at the Abramson Cancer Center at the University of Pennsylvania is testing Keytruda alongside image-guided surgery.
Durvalumab
A phase 3 trial testing durvalumab is currently recruiting at two U.S. locations: Michigan Medicine in Ann Arbor and Metro Minnesota Community Oncology Research Consortium in Saint Louis Park.
Durvalumab, the generic name for Imfinzi, is a PD-L1 checkpoint inhibitor. It works similarly to Keytruda and Opdivo by preventing the PD-L1 protein from evading the immune system’s T-cell defenses.
Researchers are combining durvalumab with chemotherapy, and the results are encouraging:
- Durvalumab plus chemotherapy led to a median survival of 20.4 months and a 44% two-year survival rate.
- Chemotherapy alone had a median survival of 12 months and a two-year survival rate closer to 25%.
Sources & Author
- Pembrolizumab in Combination With Chemotherapy and Image-Guided Surgery for Malignant Pleural Mesothelioma (MPM). U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03760575. Accessed: 10/08/19.
