Patients with NSCLC Taking Beta-Blockers While Receiving Definitive RT Have Improved Survival
Noting that “preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor,” Zhongxing Liao, MD, of the Department of Radiation Oncology at The University of Texas M.D. Anderson Cancer Center, Houston, TX, and colleagues retrospectively reviewed 722 patients at their institution with NSCLC—155 taking beta-blockers—who had received definitive RT between 1998 to 2010.
In univariate analysis, patients taking a range of different types and dosages of beta-blockers for other conditions, such as hypertension (68%) and non-hypertensive disorders (32%), most often coronary heart disease, had improved DMFS (P<0.01), DFS (P<0.01) and OS (P=0.01), but not locoregional progression-free survival (LRPFS; P=0.33) when compared with the 567 patients not taking beta-blockers. The two most commonly prescribed drugs (85% of cases) were metoprolol and atenolol.
After adjusting for age, Karnofsky performance score, stage, tumor histology, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin, multivariate analysis found beta-blocker intake to be associated with a significantly better DMFS (hazard ratio [HR] 0.67; 95% CI: 0.50-0.91; P=0.01), DFS (HR 0.74; 95% CI: 0.58-0.95; P=0.02), and OS (HR 0.78; 95% CI: 0.63-0.97; P=0.02). Median survival for patients taking beta-blockers was 23.7 months versus 18.6 months for those not on beta-blockers. No association was observed between beta-blocker use and LRPFS (HR 0.91, P=0.63).
“To our knowledge, our study represents the first analysis demonstrating a survival benefit associated with the use of beta-blockers during definitive RT for NSCLC,” Dr. Liao noted. “Our findings agree with results from previous studies suggesting that beta-blockers have a specific effect on the cascade of events that lead to metastases,” she added. “The fact that their use did not affect LRPFS suggests that the drugs affect this metastatic cascade rather than the primary tumor.”
The investigators said there were too few patients in the study to determine whether the choice of beta-blocker might be important, but that most of the study patients who did well were on a selective (β1) beta-blocker.
“Future prospective trials are needed to validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes,” they concluded.