Impact of Concomitant Use of Steroids and Immune-Checkpoint Inhibitors on Survival Outcomes in NSCLC Patients

Impact of Concomitant Use of Steroids and Immune-Checkpoint Inhibitors on Survival Outcomes in NSCLC Patients: a Multicenter Target Trial Emulation Study Utilizing EHR-based Common Data Models

The goal of this observational study is to assess the effects of systemic corticosteroid use during immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). The main question it aims to answer is:

Does the use of systemic corticosteroids during the initial continuous administration of ICI therapy affect overall survival (OS) and treatment outcomes in NSCLC patients?

Participants who received ICI therapy (nivolumab, pembrolizumab, atezolizumab, or durvalumab) between December 31, 2014, and December 31, 2021, as part of their routine medical care, will be included. Patient data will be analyzed retrospectively using clinical data from five institutions, and a 1:1 propensity score matching method will be employed to balance the baseline characteristics between groups. Statistical analyses will focus on overall survival, time-to-next-treatment (TNT), and metastasis-free survival (MFS).

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC, Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Corticosteroids (CS); Drug: Immune Checkpoint Inhibitors

Detailed Description

Purposive sampling was employed to select participants who met the specific inclusion criteria, focusing on patients diagnosed with non-small cell lung cancer (NSCLC) and treated with immune checkpoint inhibitors (ICI) (nivolumab, pembrolizumab, atezolizumab, or durvalumab) during routine clinical practice. The study specifically targets patients who received their first ICI therapy between December 31, 2014, and December 31, 2021. Participants are restricted to those diagnosed with NSCLC within 2 years prior to the date of first ICI administration. Patients with documented pregnancy within 180 days prior to the enrollment date were excluded, as were those under 18 years of age or over 100 years of age at the time of enrollment. Individuals with a history of any primary malignancy other than lung cancer within 2 years prior to the enrollment date and those who received concomitant anticancer therapies such as taxane, platinum, pemetrexed, etoposide, doxorubicin, gemcitabine, irinotecan, vinorelbine, vinblastine, or bevacizumab at the index date were also excluded. All participants were identified retrospectively from clinical data models (CDM) or electronic medical records (EMRs) across five institutions: Seoul National University Hospital, Bundang Seoul National University Hospital, Pusan National University Hospital, and the Catholic Medical Center of Korea. To minimize selection bias inherent to observational studies, time-dependent propensity score matching was performed, simulating pseudo-randomization to balance baseline characteristics between groups.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be established by constructing cohorts from patients treated at the following four hospitals: Seoul National University Hospital, Bundang Seoul National University Hospital, Pusan National University Hospital, and the Seoul Catholic Medical Center of Korea.

Description

Inclusion Criteria:

• Patients who received immune checkpoint inhibitor (ICI) therapy (nivolumab, pembrolizumab, atezolizumab, or durvalumab) for the first time between December 31, 2014 and December 31, 2021.
• Patients diagnosed with non-small cell lung cancer (NSCLC) within 2 years prior to the date of first ICI administration.

Exclusion Criteria:

• Patients with documented pregnancy within 180 days prior to the enrollment date.
• Patients who were under 18 years of age or over 100 years of age at the time of enrollment.
• Patients with a history of any primary malignancy other than lung cancer within 2 years prior to the enrollment date.
• Patients who received concomitant anticancer therapies (taxane, platinum, pemetrexed, etoposide, doxorubicin, gemcitabine, irinotecan, vinorelbine, vinblastine, or bevacizumab) at the index date.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Steroid Concomitant Group; Patients who received systemic corticosteroids concomitantly during the initial continuous administration period of immune checkpoint inhibitors.	Drug: Corticosteroids (CS); Concomitant use of immune checkpoint inhibitors and corticosteroids; Drug: Immune Checkpoint Inhibitors; Non-concomitant use of corticosteroids
Steroid Non-Concomitant Group; Patients who did not receive systemic corticosteroids concomitantly during the initial continuous administration period of immune checkpoint inhibitors.	Drug: Immune Checkpoint Inhibitors; Non-concomitant use of corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	From index date to the end of 2 years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival	Duration of survival without distant metastasis	From index date to the end of 2 years follow-up
Time-to-next-treatment	Time to treatment switch	From index date to the end of 2 years follow-up
Hospitalization	Emergency room visit or hospitalization lasting more than 3 days	From index date to the end of 2 years follow-up

Collaborators and Investigators

• Sponsor: Seoul National University
• Collaborators: Pusan National University Hospital; Seoul National University Hospital; Bundang Seoul National University Hospital; Catholic Medical Center of Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; corticosteroid; Non small cell lung cancer; ICI; Immune check point inhibitor
• 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: E-2024-4237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is an observational study using a common data model as the data source, where raw data at the individual patient level cannot be exported or managed externally.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No