Upper Respiratory Tract Infection Associated with Anti-HER2 Antibody Blockade for HER2-Positive Breast Cancer: A Bayesian Disproportionality Analysis Using Data From the FDA Adverse Event Reporting System.

Abstract

Purpose: The impact of anti-HER2 antibodies and antibody-drug conjugates (ADCs) on adverse events related to upper respiratory tract infection (URTI) in patients with HER2-positive breast cancer (BC) remains inadequately elucidated. This study sought to identify safety signals related to URTI associated with anti-HER2 antibodies and to compare the incidence and severity of these infections among patients treated with various anti-HER2 antibodies. The results may serve as a valuable reference for clinical decision-making.

Methods: Medical records of HER2-positive BC patients receiving anti-HER2 treatments from January 2015 to June 2024 were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System database. The URTI adverse events included nasopharyngitis, URTI, tonsillitis, laryngitis, rhinitis, herpangina, and pharyngitis. Four anti-HER2 treatments were identified: pertuzumab, trastuzumab deruxtecan (T-DXd), trastuzumab, and ado-trastuzumab emtansine (T-DM1). The primary endpoint was the pharmacovigilance (PV) of URTI. The secondary endpoint was the pairwise comparison of the incidence and severity of URTI.

Findings: The analysis included 458 reports. For the primary endpoint, the PV signal regarding URTI was detected in the pertuzumab group (ROR = 1.38, 95% CI: 1.16-1.64; IC₀₂₅ = 0.12) and the T-DM1 group (PRR = 2.06, 95% CI: 1.72-2.47; a = 135, χ² = 62.40; ROR = 2.07, 95% CI: 1.72-2.49; IC₀₂₅ = 0.63), whereas no such signal was observed in the trastuzumab and T-DXd groups. For the secondary endpoint, the incidence of URTI was significantly higher in the T-DM1 group than in the trastuzumab (OR = 2.19, 95% CI: 1.74-2.75), pertuzumab (OR = 1.45, 95% CI: 1.15-1.83), and T-DXd (OR = 15.16, 95% CI: 5.77-42.23) groups. The incidence of URTI associated with pertuzumab treatment was notably higher compared to trastuzumab (OR = 1.5, 95% CI: 1.21-1.88) and T-DXd (OR = 10.74, 95% CI: 3.98-28.99) treatments. In comparison to trastuzumab (OR = 8.03, 95% CI: 4.58-14.09), both pertuzumab (OR = 6.37, 95% CI: 3.72-10.93) and T-DM1 were associated with a significant increase in the severity of URTI. However, there was no significant difference in URTI severity between the trastuzumab and pertuzumab treatments.

Implications: T-DM1 treatment has a higher possibility for URTI development with higher severity, followed by pertuzumab, trastuzumab, and T-DXd. Patients receiving anti-HER2 antibody treatment, particularly T-DM1, should receive special attention regarding URTI incidence and severity.