The treatment standard of cancer has dramatically diverted with immune checkpoint inhibitors (ICI). Despite the proven clinical advantage, some tumors do not respond to ICI. The expression of PD-L1, the tumor microenvironment (TME), and the tumor mutational burden are essential to the success of ICI and are currently considered biomarkers predictive of response. Increased Beta-adrenergic receptor signaling has been shown to promote the creation of an immunosuppressive TME. The annulment of this pathway provides a more responsive TME and may enhance the activity of ICI, and the use of beta-blockade for this purpose has shown conflicting results. We investigated patients with lung cancer who concomitantly used beta-blockers (BB) and ICI, hypothesizing that blocking the beta-adrenergic pathway would impact the outcome.
We retrospectively reviewed 51 patients treated at our institution for 18 months with ICIs for non-small-cell lung cancer (NSCLC). Comparisons of overall survival and progression-free survival (PFS) were performed using Kaplan-Meier analysis with log-rank test, and a univariate regression analysis was performed with a Cox proportional hazards model.
Among the 51 patients, 11 concomitantly used beta blockers. There was no significant increase in overall survival among patients who took beta-blockers (p=0.83; 95% confidence interval, 0.33-2.47), and BB was not predictive of PFS. Although well established, our study confirmed that elevated levels of lactate dehydrogenase were associated with poorer overall survival (p=0.034, 95% confidence interval 1.000-1.005), and weight loss was predictive of PFS (p=0.019, 95% confidence interval 1.097-2.839).
In summary, this study found no evidence that BBs enhance immunotherapy effectiveness. Despite that, this was a small study, and these results should be validated in prospective clinical studies.
The authors.
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All authors have declared no conflicts of interest.