Clinical Report: Evaluating the Safety Risks of Aromatase Inhibitors

Overview

This study analyzed adverse drug events (ADEs) associated with the combination of aromatase inhibitors (AIs) and CDK4/6 inhibitors using FAERS and JADER databases. Key findings included the identification of 150 ADEs, with notable signals for neutropenia and other hematological toxicities.

Background

Aromatase inhibitors and CDK4/6 inhibitors are critical components in the treatment of hormone receptor-positive breast cancer. The safety profile of their combination therapy in real-world settings has been evaluated using data from FAERS and JADER databases.

Data Highlights

Key Findings

• 150 ADEs were identified in the FAERS database related to AI and CDK4/6 combination therapy.
• The most frequently reported ADEs included fatigue, neutropenia, and decreased white blood cell count.
• Signals for ADEs not mentioned in drug labels included skin hypopigmentation and vertigo positional.
• Combination therapy showed stronger reporting signals for neutropenia, anemia, and leukopenia compared to monotherapy.
• In the JADER database, 25 positive signals were identified, including increased alanine and aspartate aminotransferases.
• Body weight was associated with serious outcomes and hematological toxicity.

Clinical Implications

Monitoring for hematological toxicities is essential when prescribing combination therapy with AIs and CDK4/6 inhibitors.

Conclusion

The study identified significant safety concerns associated with the combination of AIs and CDK4/6 inhibitors.

Related Resources & Content

1. The ASCO Post, 2026 -- Advanced Breast Cancer: Novel CDK4/6 Inhibitor Plus an Aromatase Inhibitor
2. The ASCO Post, 2018 -- CDK 4/6 Inhibitors May Be Effective but More Toxic in Older Women
3. Clinical Rheumatology, 2022 -- Evaluating the Safety Profile of Janus Kinase Inhibitors for Rheumatoid Arthritis
4. The ASCO Post, 2015 -- Analysis Shows No Link Between Aromatase Inhibitor–Related Symptoms and Relapse-Free Survival
5. ASCO Endocrine Treatment and Targeted Therapy for HR-Positive, HER2-Negative Metastatic Breast Cancer Guideline Summary - Guideline Central
6. Risk of QTc prolongation and major cardiovascular adverse events associated with CDK4/6 inhibitors
7. ASCO Endocrine Treatment and Targeted Therapy for HR-Positive, HER2-Negative Metastatic Breast Cancer Guideline Summary - Guideline Central
8. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. | Journal of Clinical Oncology