Real-world Association Between Concomitant Beta-blocker Exposure and Anti-PD-1/PD-L1 Treatment Outcomes in Advanced Non-Small Cell Lung Cancer

A Retrospective Observational Cohort Study Evaluating the Association Between Concomitant Beta-blocker Exposure and Clinical Outcomes of Standard Anti-PD-1/PD-L1 Therapy in Advanced Non-Small Cell Lung Cancer

This retrospective real-world cohort study evaluated whether concomitant long-term beta-blocker exposure during routine clinical care was associated with clinical outcomes in patients with advanced NSCLC who received standard anti-PD-1/PD-L1 inhibitor therapy. Patients were categorized according to documented concomitant long-term beta-blocker exposure during the treatment course. Clinical outcomes, including progression-free survival, objective response rate, and overall survival, were compared between exposure groups. This was a non-interventional observational study; anti-PD-1/PD-L1 treatment and beta-blocker use were determined by routine clinical practice rather than by the study protocol.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Anti-PD-1/PD-L1 Therapy (Standard of Care); Drug: Beta-blocker (Concomitant Exposure)

Detailed Description

Background:

Emerging evidence suggests that beta-adrenergic signaling may contribute to T-cell dysfunction and resistance to immune checkpoint blockade. This retrospective real-world cohort study was designed to investigate whether concomitant long-term beta-blocker exposure during routine clinical care was associated with treatment outcomes in patients with advanced NSCLC receiving standard anti-PD-1/PD-L1 inhibitor therapy.

Study Design:

Clinical data and follow-up information were collected retrospectively from eligible patients treated in routine clinical practice at the Affiliated Hospital of Nantong University during the predefined study period. Patients were categorized into exposure cohorts according to whether they had documented concomitant long-term beta-blocker use during anti-PD-1/PD-L1 treatment. The study did not assign treatment or medication exposure; all therapies and concomitant medications were prescribed according to standard clinical indications and physician judgment.

Objectives:

The primary objective was to assess the association between concomitant long-term beta-blocker exposure and progression-free survival. Secondary objectives included evaluation of objective response rate and overall survival. The study was intended to provide real-world observational evidence regarding the clinical relevance of beta-blocker exposure in the setting of standard anti-PD-1/PD-L1 therapy for advanced NSCLC.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nantong, Jiangsu, China, 226000
      • Department of Pharmacy, Affiliated Hospital of Nantong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This retrospective study included eligible patients with advanced non-small cell lung cancer who received standard anti-PD-1/PD-L1 inhibitor therapy in routine clinical practice at the Affiliated Hospital of Nantong University during the predefined study period. Clinical records and follow-up information were collected retrospectively. Patients were categorized into exposure cohorts according to documented concomitant long-term beta-blocker use during the anti-PD-1/PD-L1 treatment course.

Description

Inclusion Criteria:

• Age 18 years or older;
• Histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer;
• Received standard anti-PD-1/PD-L1 inhibitor therapy during routine clinical care;
• Available baseline clinical records and follow-up data sufficient for assessment of treatment exposure and clinical outcomes;

Exclusion Criteria:

• Incomplete baseline clinical records or follow-up data that preclude assessment of treatment exposure or clinical outcomes;
• Concomitant participation in an interventional therapeutic clinical trial affecting the same treatment course, if applicable;
• Other major clinical conditions or competing malignancies that preclude valid outcome assessment, according to the prespecified study protocol

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard Anti-PD-1/PD-L1 Therapy Without Long-term Beta-blocker Exposure; Patients with advanced NSCLC who received standard anti-PD-1/PD-L1 inhibitor therapy during routine clinical care and had no documented long-term beta-blocker exposure during the relevant treatment period.	Drug: Anti-PD-1/PD-L1 Therapy (Standard of Care); Standard anti-PD-1/PD-L1 inhibitor therapy administered as part of routine clinical care. Treatment regimen, schedule, and duration were determined by treating physicians according to standard practice and were not assigned by the study.
Standard Anti-PD-1/PD-L1 Therapy With Concomitant Long-term Beta-blocker Exposure; Patients with advanced NSCLC who received standard anti-PD-1/PD-L1 inhibitor therapy during routine clinical care and had documented concomitant long-term beta-blocker exposure during the relevant treatment period. Beta-blockers were prescribed for routine clinical indications and were not assigned by the study protocol.	Drug: Anti-PD-1/PD-L1 Therapy (Standard of Care); Standard anti-PD-1/PD-L1 inhibitor therapy administered as part of routine clinical care. Treatment regimen, schedule, and duration were determined by treating physicians according to standard practice and were not assigned by the study.; Drug: Beta-blocker (Concomitant Exposure); Documented concomitant long-term beta-blocker use during the anti-PD-1/PD-L1 treatment course as prescribed for routine clinical indications. Beta-blocker exposure was not assigned by the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Progression-free survival is defined as the time from initiation of anti-PD-1/PD-L1 therapy to the first documented disease progression or death from any cause, whichever occurs first.	From initiation of anti-PD-1/PD-L1 therapy to first documented disease progression or death from any cause, assessed up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate is defined as the proportion of patients achieving complete response or partial response according to RECIST version 1.1 based on available radiologic assessments in routine clinical care.	Best overall response during the first 12 months after initiation of anti-PD-1/PD-L1 therapy
Overall Survival	Overall survival is defined as the time from initiation of anti-PD-1/PD-L1 therapy to death from any cause.	From initiation of anti-PD-1/PD-L1 therapy to death from any cause, assessed up to 36 months

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University
• Collaborators: The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
• Investigators: Study Director: Zhiyuan Tang, Doctor, Affilication Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): May 31, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; PD-1; PD-L1; Beta-blocker; Real-world Study
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agents; Adrenergic Antagonists; Health Services Administration; Health Care Quality, Access, and Evaluation; Pharmacologic Actions; Chemical Actions and Uses; Quality of Health Care; Quality Indicators, Health Care; Adrenergic beta-Antagonists; Standard of Care
• Other Study ID Numbers: 2022-L071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No