Palbociclib (Ibrance®): A Comprehensive Monograph on the First-in-Class CDK4/6 Inhibitor for HR+/HER2- Breast Cancer

Executive Summary & Drug Profile

Overview of Palbociclib

Palbociclib represents a landmark achievement in the targeted therapy of breast cancer. Developed by Pfizer and marketed under the brand name Ibrance®, it is the first-in-class, orally available, small molecule drug that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6).[1] Its introduction heralded a paradigm shift in the management of the most common subtype of advanced breast cancer: hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) disease.[1]

Palbociclib is not used as a monotherapy but as a crucial component of combination treatment. It is prescribed with an aromatase inhibitor, such as letrozole, as an initial endocrine-based therapy for postmenopausal women or men. Alternatively, it is combined with the selective estrogen receptor degrader fulvestrant for patients whose disease has progressed after a prior course of endocrine therapy.[5]

The clinical development and regulatory approval of palbociclib were predicated on its ability to deliver a profound and consistent benefit in progression-free survival (PFS), effectively doubling the time until disease worsening in pivotal clinical trials. This remarkable efficacy established CDK4/6 inhibition as a new standard of care. However, a defining characteristic of palbociclib's clinical profile is that this substantial PFS benefit has not translated into a statistically significant improvement in overall survival (OS) in its key trials. This distinction remains a central point of clinical discussion, scientific debate, and economic evaluation, especially in comparison to later-in-class competitors.[1]

Chemical and Physical Properties