Follow-Up after adjuvanT CDK4/6i Use in oldeR brEst cancer patients - aspects on geriatric screening, toxicities, and quality of life (FUTURE): A prospective observational cohort study

INTRODUCTION: Age alone should not preclude systemic therapy in early breast cancer, although older patients often present with comorbidities and increased susceptibility to treatment-related toxicity. Geriatric screening could add information to better individualize their adjuvant treatment. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have demonstrated efficacy as adjuvant therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. However, older adults were underrepresented in pivotal clinical trials. This study aims to evaluate the value of geriatric screening among patients aged ≥70 years receiving adjuvant CDK4/6i, focusing on its association with quality of life, toxicity risk, relative dose intensity (RDI), and clinical outcomes. MATERIALS AND METHODS: This is a Swedish multicenter, prospective observational cohort study including approximately 200 patients aged ≥70 years diagnosed with early-stage ER+/HER2- breast cancer starting adjuvant CDK4/6i. Baseline assessments will include the Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) geriatric screening tools. Quality of life will be evaluated using EORTC QLQ-C30 and ELD14 questionnaires at predefined intervals. Moreover, clinical endpoints include grade ≥3 toxicity (as defined by CTCAE 5.0), CDK4/6i discontinuation, dose modifications, and hospitalization rates. Dose intensity will be assessed via RDI. Long-term outcomes, including breast cancer recurrence and breast cancer-specific survival, and overall survival, will be collected at 3-, 5-, and 10-year follow-up. DISCUSSION: Older patients remain underrepresented in clinical trials of adjuvant CDK4/6i, leading to uncertainty regarding real-world benefits and tolerability in this population. International guidelines advocate the integration of geriatric assessment in oncology to support tailored treatment decisions, yet its use remains limited in everyday clinical practice. This study seeks to assess the feasibility and clinical impact of geriatric assessments in routine care of older breast cancer patients receiving adjuvant CDK4/6i. Findings will provide essential data on the relationship between frailty and quality of life, treatment tolerance, dosing, and long-term outcomes, thereby potentially informing future clinical guidelines and improving personalized management for older patients with early breast cancer. TRIAL REGISTRATION: Registered in clinicaltrials.gov NCT Number: NCT07273357.