Pharmacovigilance in EGFR-Targeted Breast Cancer Therapy: Monitoring Safety Beyond the Bench
Keywords:
Pharmacovigilance, EGFR inhibitors, breast cancer, adverse drug reactions, skin rash, diarrhea, hepatotoxicity, cardiotoxicity, FAERS, WHO-VigiBase, social media, signal detection, real-world evidence, tolerabilityAbstract
Background: Epidermal growth factor receptor (EGFR) inhibitors, including tyrosine kinase inhibitors like lapatinib and neratinib, have transformed breast cancer management, particularly in HER2-positive and triple-negative subtypes where EGFR overexpression drives aggressive disease. However, their adoption is tempered by class-effect adverse drug reactions (ADRs), including skin rash, diarrhea, hepatotoxicity, and cardiotoxicity, which compromise tolerability and adherence. Traditional clinical trials underrepresent real-world complexities, necessitating robust pharmacovigilance to monitor safety beyond preclinical and controlled settings.
Objective: This narrative review synthesizes evidence on ensuring the safety and tolerability of EGFR inhibitors in breast cancer, emphasizing ADR profiles and innovative signal detection strategies to inform clinical practice and regulatory oversight.
Key Methods: A comprehensive literature synthesis was conducted using PubMed, Embase, and Scopus (2010–2025), supplemented by analyses of FAERS (U.S. spontaneous reports) and WHO-VigiBase (global database). Social-media mining via natural language processing of platforms like X (formerly Twitter) was integrated to capture patient-reported outcomes. Thematic extraction focused on ADR incidence, management, and signal trends.
Main Findings: Skin rash affects 40–80% of patients (grade 3–4: 5–15%), diarrhoea 30–95% (up to 40% severe with neratinib), hepatotoxicity 5–15% (higher in Asian cohorts per VigiBase), and cardiotoxicity 3–10% (ROR >2 in FAERS for lapatinib). Disproportionality analyses reveal temporal escalations (e.g., >1,500 annual reports 2022–2024), while social-media data uncovers unreported nuances, such as rash-related emotional distress (72% of lapatinib posts) and diarrhoea coping strategies (65% endorsing prophylaxis). Hybrid approaches correlate digital spikes with database signals, estimating 25% underreporting.
