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Beta-blockers improved DFS, OS in patients with NSCLC
Beta-blocker use was associated with improved locoregional PFS, distant metastasis-free survival, DFS and OS in a cohort of patients with non–small cell lung cancer, according to study results.
Previous clinical studies have indicated that beta-blockers — typically prescribed for hypertension or heart disease — may promote antitumor activities, reducing metastasis, tumor recurrence and cancer-specific mortality for patients with breast cancer, as well as increasing survival time for patients with melanoma.
However, there is little available data regarding the effects of beta-blockers on lung cancer progression or metastasis in vivo.
“Despite recent improvements in radiotherapy and chemotherapy for non–small cell lung cancer, the prognosis of this disease is poor, with less than 15% of patients surviving for 5 years after diagnosis,” Daniel Gomez, MD, assistant professor in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “A major cause of death is the process of metastasis, when cancer cells travel from the original tumor to other parts of the body. Therefore, we urgently need to find new ways of blocking the development of metastases in these patients.”
To determine whether the use of beta-blockers reduced the rates of disease progression and improved OS in locally advanced NSCLC, Gomez and colleagues retrospectively reviewed 722 patients with NSCLC who had received definitive radiotherapy at MD Anderson Cancer Center.
Patients in this cohort were selected from a large clinical database that included detailed patient demographic data, chemotherapy data, inclusive tumor details and radiotherapy data, as well as outcome and mortality data.
In univariate analysis, when compared with patients who did not receive beta-blockers (n=567), patients who were administered beta-blockers (n=155) exhibited improved distant metastasis-free survival (P<.01), DFS (P<.01) and OS (P=.01), but not locoregional PFS (P=.33).
However, in multivariate analysis, beta-blocker intake was associated with a significantly improved distant metastasis-free survival (HR=0.67; P=.01), DFS (HR=0.74; P=.02) and OS (HR=0.78; P=.02) with adjustment for stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, chronic obstructive pulmonary disease, hypertension and aspirin use.
Researchers observed no relationship between beta-blocker use and locoregional PFS (HR=0.91; P=.63).
“Our results suggest that the use of beta-blockers during radiotherapy may help to prevent the formation of metastases and could lead directly or indirectly to improved care for patients with non–small cell lung cancer,” Gomez said in a press release. “As far as we are aware, our study is the first analysis to show a survival benefit associated with the use of beta-blockers during definitive radiotherapy in patients with NSCLC.
“However, prospective studies are needed to investigate these findings further and to discover whether improved survival is affected by when and for how long patients need to take beta-blockers,” Gomez added. “We are excited about using our study as a starting point for further investigations.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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The results of this detailed retrospective study suggest that commonly prescribed beta-blocker medications may improve the metastasis-free survival and OS of patients with non–small cell lung cancers who have completed definitive thoracic radiation therapy, but interestingly have no effect on locoregional disease progression. This supports the authors’ hypothesis, which is based on preclinical data that demonstrated catecholamine exposure leads to cancer spread and can be mitigated by beta-blockade.
Although this data is intriguing and delves into a sorely unmet need in lung cancer biology, namely the mediators of metastasis in early-stage non–small cell lung cancers, the results of any retrospective study must be interpreted with caution. If validated, this finding could have great implications for lung cancer care. I look forward to future studies validating this finding in similar cohorts of patients who have received definitive radiation therapy and perhaps in patients with resected non–small cell lung cancers who should similarly benefit given the biological rationale for this intervention.
Perspective
Back to TopThe study reported by Wang et al. is a thought-provoking retrospective review which is the first to demonstrate a potential association of the use of beta-blockers with reduced rates of metastasis and improved overall survival after definitive radiation for lung cancer. This investigation is based upon pre-clinical data linking beta-adrenergic signaling to several biological processes associated with metastasis, and previous retrospective data in other cancers linking beta-blockers with outcomes. The size and quality of the MD Anderson database allows this question to be addressed, though further retrospective and perhaps higher level evidence is needed before beta-blockers are adopted as standard of care.
Potentially confounding factors include the observation that for this study population patients on beta-blockers were older, had less advanced disease, and were less likely to be treated with chemotherapy, though the advantage of beta blockers held on multivariate analysis. Given the magnitude of the potential association of beta-blockers on metastasis and survival, compared with the relatively few significant recent advances in survival in the lung cancer population, further study is certainly warranted.