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European researchers may have found the key to making immunotherapy drugs such as Opdivo and Keytruda more effective for a larger percentage of patients with malignant pleural mesothelioma.
Statins may be the answer.
While treatment with these advertised immunotherapy drugs has worked wonders for some, the majority of mesothelioma patients get little or no benefit in fighting this cancer without treatment.
That could change soon.
In a recent study, doctors found that patients with pleural mesothelioma receiving high-intensity statins in combination with Opdivo experienced dramatic improvements in overall response rate, progression-free survival, and median overall survival, per compared to those receiving only the immunotherapy drug.
The European Journal of Cancer will publish the study in its February 2021 issue. The researchers are from Italy and the Netherlands.
“Our study potentially opens up new scenarios for mesothelioma patients in the future,” said lead author Dr Rossana Berardi of the Universita Politecnica delle Marche in Ancona, Italy at the Mesothelioma Center of Asbestos. com. “The impact of statins was significant.”
Make immunotherapy more effective
Statins are best known for their use in lowering high cholesterol levels in otherwise healthy people. Their potential benefit as an anticancer adjuvant is still debated and studied.
This study, which included both patients with pleural mesothelioma and advanced non-small cell lung cancer, found potential synergy with immunotherapy drugs.
Opdivo and Keytruda, generically called nivolumab and pembrolizumab, respectively, are called PD-1 inhibitors, drugs that prevent a protein from stopping the immune response to cancer cells.
“Statins can lead to prolonged antigen retention on the cell membrane and enhance antigen presentation to T cells, thus suggesting potential synergy with PD-1 inhibitors,” the authors wrote. “The anti-tumor effect of statins could be attributed to an indirect immunotherapeutic effect.”
The 82 pleural mesothelioma patients in the study were from Erasmus Medical Center in Rotterdam, the Netherlands, and were part of the expanded access program for nivolumab. They were all receiving second or third line treatment.
Improvement with statins was considerable
The overall response rate was 22% versus 6% for those receiving statins with nivolumab versus those not receiving statins. The progression-free survival advantage was 6.7 months versus 2.3 months, respectively.
Median overall survival was not reached at the end of the study for those receiving statins compared to six months for those who did not.
When patients with non-small cell lung cancer were included, the results were almost as impressive with statins as with non-statins:
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Overall response rate: 32% vs. 18%
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Median progression-free survival: 6.7 months vs. 2.9 months
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Median overall survival: 13.1 months versus 8.7 months
In a control group of mesothelioma patients who used only chemotherapy with statins, no improvement in progression-free survival or overall survival was found, emphasizing the belief in a synergistic effect with immunotherapy.
Immunotherapy alone for mesothelioma has failed
The recent use of immunotherapy drugs for pleural mesothelioma has been both encouraging and at times disappointing.
In October, the immunotherapy combination of Opdivo and Yervoy became the first combination drug in 16 years to be approved by the FDA for the first-line treatment of pleural mesothelioma.
Then, in June, Keytruda was approved for an unresectable disease that had progressed after first-line treatment with no further options.
At the same time, the two drugs only worked effectively for a small percentage of mesothelioma patients with specific molecular alterations. They worked most effectively when combined with other drugs that elicit a synergistic response.
The study authors also noted that high-intensity statins that often come with increased side effects were more effective than low-intensity ones.
“If our results are confirmed prospectively, statins could represent an optimal strategy for drug reuse in combination with anti-PD-1 therapy to improve outcomes in patients with thoracic malignancies, including mesothelioma,” said said Berardi.
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