The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab

Yasmin Leshem, Tal Etan, Yardenna Dolev, Alla Nikolaevski-Berlin, Mor Miodovnik, Sivan Shamai, Ofer Merimsky, Ido Wolf, Ofer Havakuk, Maor Tzuberi, Yan Topilsky, Shmuel Banai, Zach Rozenbaum, Michal Laufer-Perl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (β1)-selective -blocker (β1B) in lung cancer patients is unknown. Objective: To evaluate the effect of β1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. Methods: We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. Results: Of 200 eligible patients, 53 (27%) were pretreated with β1B. Patients in the β1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-β1B group, patient pretreated with β1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline β1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32–2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18–2.75, p = 0.007). Conclusions: The use of baseline β1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.

Original languageEnglish
Article number131642
JournalInternational Journal of Cardiology
Volume397
DOIs
StatePublished - 15 Feb 2024

Keywords

  • Beta 1-selective
  • Beta-blockers
  • Immunotherapy
  • Lung cancer
  • NSCLC

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