CDK 4/6 inhibitors mired in uncertainty in HR positive and HER2 negative early breast cancer

Highlights

• HR+/HER2-early BC patients have continuous risk of relapse and need new therapies

• Current short follow-up precludes any final conclusion re. adjuvant CDK4/6 inhibitors

• The proportional hazard assumption was hampered by the low number of events

• Wide point estimate 95%CI translated into imprecise number needed to treat (NNT)

• Besides efficacy, toxicity, compliance and cost are issues to consider in decision-making

• Research efforts need to continue to establish CDK4/6 inhibitor predictive biomarkers

Abstract

Cell-cycle abnormalities are common in estrogen receptor- and/or progesterone receptor-positive, and HER2-non-overexpressing (HR+/HER2-) breast cancer, and have long been considered potential therapeutic targets. Cyclin-dependent kinase (CDK) 4/6 inhibitors have dramatically changed the therapeutic management of HR+/HER2-advanced breast cancer by prolonging progression-free and overall survival when given in combination with endocrine therapy. In this article, available data from PALLAS and monarchE trials regarding the efficacy and toxicity of adjuvant combined therapy with CDK 4/6 inhibitors and endocine therapy in HR+/HER2-early breast cancer are reviewed, and relevant issues including study hypothesis, patient selection, and duration of follow-up are discussed.