Adverse Event Profiling and Comparative Analysis of HER2-targeting Antibody-drug Conjugates Using Pharmacovigilance...

Area of Science:

• Pharmacovigilance and Drug Safety
• Oncology
• Immunotherapy

Background:

• Anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) are crucial in cancer therapy.
• The safety profiles of T-DM1 and T-DXd require comprehensive characterization.
• Real-world adverse event data from large databases can elucidate safety signals.

Purpose of the Study:

• To compare the adverse event profiles of T-DM1 and T-DXd.
• To identify distinct safety signals associated with each HER2 ADC.
• To validate findings against existing clinical trial data.

Main Methods:

• Analysis of the Japanese Adverse Drug Event Report (JADER) database (April 2004-April 2025).
• Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database (Q1 1997-Q1 2025).
• Inclusion of all reported cases for T-DM1, T-DXd, trastuzumab, and pertuzumab, irrespective of severity.

Main Results:

• Hepatobiliary disorder signals identified for T-DM1.
• Hematotoxicity and infection-related signals, including sepsis and Pneumocystis jirovecii pneumonia (PJP), prominent for T-DXd.
• Interstitial lung disease observed for both agents; cardiac disorder signals for trastuzumab, pertuzumab, and T-DM1, but not T-DXd.
• T-DXd associated nausea and myelosuppression reported early (<40 days), PJP later (median 90 days).

Conclusions:

• T-DM1 and T-DXd exhibit distinct adverse event profiles, consistent with clinical trial findings.
• Hepatobiliary disorders are characteristic of T-DM1; hematotoxicity and infections are characteristic of T-DXd.
• PJP represents a significant, later-onset infection-related signal for T-DXd, warranting clinical attention.