Interstitial Pneumonitis Associated With EGFR-TKI and Combined With PD-1/PD-L1

Completed

• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Interventions: Drug: EGFR-TKI; Drug: PD-1/PD-L1 inhibitor; Drug: EGFR-TKI combined with PD-1/PD-L1

• Registration Number: NCT07036016
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

Importance:

EGFR tyrosine kinase inhibitors (EGFR-TKIs) and PD-1/PD-L1 immune checkpoint inhibitors are widely used in the treatment of non-small cell lung cancer (NSCLC). However, the safety profile of their combination-particularly the risk of interstitial pneumonitis (IP)-remains unclear.

Objective:

To evaluate the incidence and risk of interstitial pneumonitis associated with EGFR-TKIs when combined with PD-1/PD-L1 inhibitors, using real-world pharmacovigilance data.

Design, Setting, and Participants:

This retrospective observational study analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS) between January 1, 2015, and December 31, 2024. A total of 67,818 NSCLC cases were included, categorized by treatment with EGFR-TKIs, PD-1/PD-L1 inhibitors, combined therapy, or the other therapies.

Exposure:

NSCLC patients receiving EGFR-TKI PD-1/PD-L1 inhibitors, combined therapy, or the other therapies were compared to those not receiving such treatment.

Main Outcome and Measures:

Incidence of reported interstitial pneumonitis and adjusted odds ratios (aORs) derived from multivariable logistic regression analyses.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-01
• Primary Completion: 2024-12-31
• Study Completion: 2025-05-01
• Status Verified: 2025-06
• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-17
• Last Update Submitted: 2025-06-17
• Study First Posted: 2025-06-25
• Last Update Posted: 2025-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67818

Inclusion Criteria

• Patients with non-small cell lung cancer (NSCLC).
• Received at least one EGFR-TKI (gefitinib, erlotinib, afatinib, osimertinib). Or received at least one PD-1/PD-L1 inhibitor (nivolumab, pembrolizumab, atezolizumab, durvalumab). Or received combination therapy with both EGFR-TKIs and PD-1/PD-L1 inhibitors. Or received the other therapies.
• Cases reported in the FDA Adverse Event Reporting System (FAERS) between January 1, 2015, and December 31, 2024.

Exclusion Criteria

• Non-NSCLC Indications: Cases not related to NSCLC (e.g., other cancer types).
• Incomplete Treatment Data: Patients with missing or unclear treatment exposure information (e.g., use of unrelated therapies).
• Duplicate Reports: Duplicate adverse event reports were excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
EGFR-TKI	EGFR-TKI	-
PD-1/PD-L1	PD-1/PD-L1 inhibitor	-
EGFR-TKI combined with PD-1/PD-L1	EGFR-TKI combined with PD-1/PD-L1	-

Primary Outcome Measures

Name	Time	Method
Incidence of reported interstitial pneumonitis and adjusted odds ratios (aORs) derived from multivariable logistic regression analyses.	From January 1, 2015, and December 31, 2024