A new study published in JAMA Network Open gives hope that a specific class of cholesterol-lowering drugs may boost the effectiveness of immunotherapy in ways that could benefit mesothelioma patients. Researchers found that patients with certain cancers treated with immune checkpoint inhibitors—the same class of drugs FDA-approved for mesothelioma—who also took PCSK9 inhibitors had a 31% reduction in mortality risk compared to patients taking high-intensity statins.
Class of Cholesterol Medication May Enhance Mesothelioma Immunotherapy’s Effects
Though mesothelioma patients were not among the study’s cohort, those who were included were all being treated with PD-(L)1 immune checkpoint inhibitors, the same class of drugs approved by the FDA as a standard treatment for mesothelioma, and with PCSK9 inhibitors. PCSK9 is a protein that regulates LDL receptors. People who have high levels of PCSK9 are more likely to have high cholesterol. Dr. Changchuan Jiang and colleagues at the University of Texas Southwestern Medical Center examined patients with non-small cell lung cancer, melanoma, and renal cell cancer, and found that PCSK9 inhibitors, which are already FDA-approved to lower LDL cholesterol, may also overcome the immunotherapy resistance that can negatively impact cancer outcomes.
Despite significant advances in cancer immunotherapy, many cancer patients, including those with mesothelioma, don’t respond to its use, and others do but don’t have lasting responses. The researchers’ preclinical studies suggest that in addition to causing high cholesterol, PCSK9 may boost immunotherapy resistance by allowing tumor cells to evade the immune system, while PCSK9 inhibition may reverse that resistance.
Mesothelioma Patients May Benefit, Without Any Cardiovascular Impact
The study examined 478 patients, 239 of whom were using PCSK9 inhibitors and 239 who were using high-intensity statins. All had been treated with immune checkpoint inhibitors. During a median follow-up of 22 months, 99 patients in the PCSK9 inhibitor group died of their cancer compared to 129 in the statin group, reflecting a 31% reduction in mortality. The two-year survival rates were 62% for PCSK9 inhibitor patients versus 51% for statin patients. This is a meaningful difference, especially for mesothelioma patients who face a poor prognosis.
Critically, the survival benefit appeared to be independent of cardiovascular impact, with no significant difference in major adverse heart events between groups. Patients using the PCSK9 inhibitors also required 35% fewer visits to the emergency room, had 27% fewer hospitalizations, and required 32% less critical care. According to Dr. Jiang, “A very important paper by a group at Duke showed pretty strong translational data suggesting a lot of tumor cells evade immune checkpoint inhibitors by using this pathway, and PCSK9 inhibitors can be used to reverse this resistance.”
Mesothelioma is a challenging disease, and each discovery offering hope for longer survival and improved quality of life is important. If you or someone you love has been diagnosed with this rare and challenging disease, contact the Patient Advocates at Mesothelioma.net to learn how we can help. We can be reached at 1-800-692-8608.
