Lung cancer patients who take beta-adrenergic receptor antagonists (beta-blockers) may survive longer and have a lower rate of tumor spread.
This is the result of a retrospective study of 722 non–small-cell lung cancer (NSCLC) patients published in Annals of Oncology.
NSCLC patients who were taking beta-blockers for an independent condition during their radiotherapy cancer treatment had a 22% improved survival compared to patients not taking beta-blockers after adjustment for factors such as age, disease stage, and concurrent chemotherapy. Patients on beta-blockers survived 23.7 months compared to 18.6 months for patients who were not taking the drugs.
Beta-blockers target the beta receptors on heart muscles and smooth muscles and are commonly prescribed for hypertension, cardiac arrhythmias, and as secondary prevention after a heart attack.
Zhongxing Liao, MD, and Daniel Gomez, MD, both from the department of radiation oncology at the MD Anderson Cancer Center in Houston, and colleagues compared outcomes of those NSCLC patients being treated with radiotherapy as their main line of treatment who were either not taking or regularly taking beta-blockers to treat another unrelated condition.
While beta-blockers didn’t influence the locoregional progression-free survival, the 155 patients on beta-blockers at the time of their radiotherapy lung cancer treatment had better distant metastasis-free survival (P < .01) and disease-free survival (P < .01) compared to the 567 patients not taking beta-blockers.
When adjusting for other factors including age, performance status, histology, concurrent chemotherapy, total tumor volume, stage of disease, those on beta-blockers did better in terms of distant metastasis-free survival (hazard ratio [HR], 0.67; P = .01), disease-free survival (HR, 0.74; P = .02), and overall survival (HR, 0.78; P = .02). There was no correlation, however, with locoregional progression-free survival (HR, 0.91, P = .63).
There is nothing unique about the combination of radiation therapy as a modality and beta-blocker usage, according to Gomez. “It would not be unreasonable to propose that these results may be extrapolated to other modalities, such as chemotherapy or surgery.”
This study is the first to show a link between improved survival and beta-blocker usage in lung cancer patients. Similar retrospective results have been shown for breast cancer, including triple-negative breast cancer and melanoma. Previous studies have also shown that beta-blockers may have antitumor activity, including in lung cancer models.
One previous retrospective lung cancer study did not show any benefit of beta-blockers on patient outcomes. The authors note that the study did not take into account any other clinical factors other than beta-blocker usage and excluded patients with chronic obstructive pulmonary disease or coronary heart disease, both of which are common among cancer patients.
Further studies, including prospective trials are needed to follow up and confirm these results. Weakness of the current study include missing data of other medications the patients may have taken during their cancer, data from only a single institution, and lack of data on beta-blocker usage prior to and post-radiation therapy.
How beta-blockers may affect metastasis is not clear but may help to suppress chronic stress conditions that result from stress hormones, which have been shown to facilitate the spread of tumor cells from their primary site of origin.
“We hypothesize that the mechanism of this benefit is by blocking the beta-adrenergic signaling pathway,” said Gomez. It has been demonstrated in both tissue culture and animal model experiments that blocking this pathway can affect the spread and growth of tumors.
“Future molecular studies will help us to understand if the mechanism that we propose is correct, and thus if beta-blockers are indeed directly affecting the aggressiveness of this malignancy, or if these findings are due to the activation or inhibition of another pathway,” said Gomez.