The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study

Time to Treatment Discontinuation (TTD)

The purpose of this study is to generate evidence on an alternative dosing strategy for
 CDK4/6 inhibitors to help more patients with MBC (age ≥ 65 years) tolerate side effects and
 stay on treatment longer, to derive the most clinical benefit from these drugs.
 
 The primary objective of the CDK Study is to compare TTD on the approved dosing for
 palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally
 daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same
 schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg
 or 200 mg) and escalating the dose if well-tolerated in combination with provider/patient
 choice endocrine therapy (AI or fulvestrant) in patients age 65 or older with HR+/HER2- MBC.
 The secondary and exploratory objectives will generate evidence needed to personalize
 treatment decisions by comparing patient-centric secondary outcomes and evaluating baseline
 factors.
 
 Together with their treating physician, participants will choose the CDK4/6 inhibitor
 (palbociclib or ribociclib) and which endocrine therapy (aromatase inhibitor or fulvestrant)
 of their choice but will be randomized to either Arm 1 (indicated dosing) or Arm 2 (titrated
 dosing).