Metastatic Melanoma Patients May Benefit From Beta Blockers

Beta blockers appear to affect immune cells and improve immune function, and now investigators are reporting that beta blockers may play an important role in boosting immunotherapy in patients with metastatic melanoma. Researchers at Penn State University conducted a retrospective study and found that melanoma patients who received immunotherapy while taking a pan beta blocker lived longer than patients who received immunotherapy alone.

The findings, which were published in the journal OncoImmunology, have prompted a new clinical trial of propranolol and pembrolizumab in combination for patients with metastatic melanoma. “We hope that the trial shows in a prospective fashion that a cheap, safe, and readily available drug such as propranolol can add value to expensive immunotherapies in terms of response and survival,” said Joseph Drabick, MD, a professor of medicine at Pennsylvania State University in Philadelphia, Pennsylvania. 

He said these new findings suggest that the immune system is very complex and interacts with many other systems in the body such as the autonomic nervous system. In studies developed by Kathleen Kokolus, MD, a postdoctoral fellow at Penn State, the researchers analyzed data from 195 metastatic melanoma patients who were treated with immunotherapy between 2000 and 2015. Among the 195 patients, 62 were also taking beta blockers. The researchers compared survival between the patients taking beta one–selective blockers, pan beta blockers, and no beta blockers.

Although there was little difference in how long patients taking beta one–selective blockers or no beta blockers lived, the results indicated that patients taking pan beta blockers lived significantly longer. Approximately 70% of patients receiving pan beta blockers were still alive compared to about 25% of those taking beta one–selective blockers or no beta blockers at 5 years post-immunotherapy.

The team also performed a parallel experiment in mice with melanoma. They treated the mice with immunotherapy with or without a pan beta blocker (propranolol). The researchers found that the propranolol significantly delayed tumor growth and increased survival when combined with immunotherapy. “Our findings suggest that administration of pan beta blockers could improve the long-term benefits of immune-based therapies for patients with advanced-stage melanoma,” Dr. Kokolus told Cancer Network.

These new findings are especially encouraging because they revealed that an already Food and Drug Administration–approved agent with proven safety could quickly be introduced into clinical practice. Patients with metastatic melanoma often have a poor prognosis. Immunotherapies have been promising, but they have also been hampered by response rates of less than 35%. Now, those response rates may change thanks to a generic drug. “This work validates the idea that old agents may be repurposed for new indications that are totally different from the disease states for which they had been designed,” Dr. Drabick told Cancer Network.