Treatment Sequencing and Patient Adherence With CDK4/6 Inhibitors

Treatment Sequencing and Patient Adherence With CDK4/6 Inhibitors

Multimodal Treatment Sequencing in Early-Stage Disease

In the early-stage setting, CDK4/6 inhibitors are incorporated using a stepwise approach within comprehensive multimodal therapy. Treatment typically follows a sequential pattern: surgery and radiation therapy first, followed by initiation of aromatase inhibitor or hormonal therapy with patient stabilization, then addition of CDK4/6 inhibitor once endocrine therapy is well-tolerated. Bone-directed agents are subsequently introduced after other therapies are established. For BRCA-positive patients, olaparib therapy is typically completed first (1 year) before initiating CDK4/6 inhibitor therapy. This methodical approach allows for identification and management of treatment-specific adverse effects while optimizing patient tolerance across multiple therapeutic modalities.

Simplified Sequencing in Metastatic Disease

Metastatic disease management follows a more straightforward approach with concurrent initiation of endocrine therapy and CDK4/6 inhibitor as first-line treatment. Based on overall survival data, ribociclib is frequently preferred, with aromatase inhibitor started first followed closely by CDK4/6 inhibitor addition once medication access is secured. Treatment sequencing also incorporates the potential for switching between CDK4/6 inhibitors or modifying endocrine therapy backbone in patients experiencing mild progression, utilizing available clinical trial data to guide decision-making in these challenging scenarios.

Adherence Challenges and Health Care Team Strategies

Patient adherence varies significantly between treatment settings, with metastatic patients generally demonstrating better compliance due to symptomatic disease and direct survival impact. Early-stage patients present greater adherence challenges as they are asymptomatic post-treatment and may question continued therapy necessity while experiencing quality-of-life impacts. Critical adherence strategies include comprehensive shared decision-making, detailed toxicity education using specific grading criteria (grade 1 vs grade 2 definitions), and proactive symptom management protocols. The initial 90-day period represents the highest risk for discontinuation, requiring intensive health care team coordination with multiple patient touchpoints. Long-term success demands sustained longitudinal monitoring and ongoing education throughout potentially years-long treatment courses, utilizing the entire health care team including pharmacists to maintain consistent patient engagement and support.