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

Huazhong University of Science and Technology

Status: Completed

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Treatments: Drug: EGFR-TKI; Drug: PD-1/PD-L1 inhibitor; Drug: EGFR-TKI combined with PD-1/PD-L1

Study type: Observational

Funder types: Other

Identifiers

NCT07036016

WHUH_2025_06

Details and patient eligibility

About

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.

Enrollment: 67,818 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

67,818 participants in 3 patient groups

EGFR-TKI

Treatment:

Drug: EGFR-TKI

PD-1/PD-L1

Treatment:

Drug: PD-1/PD-L1 inhibitor

EGFR-TKI combined with PD-1/PD-L1

Treatment:

Drug: EGFR-TKI combined with PD-1/PD-L1