Association Between Dose Reduction of Cyclin-dependent Kinase 4/6 Inhibitors and Survival in Advanced Breast Cancer:...

The integration of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the treatment regimen for advanced breast cancer (BC), specifically oestrogen receptor-positive (ER+) subtypes, marks a significant stride in oncological therapy. These inhibitors have demonstrated substantial clinical benefits and are generally well tolerated compared to other targeted therapies. Our study evaluated the effects of dosage reductions on progression-free survival (PFS) and overall survival (OS) in patients undergoing CDK4/6 inhibitor therapy.

We conducted an exhaustive literature review across several databases, including PubMed, Embase, and Cochrane, considering studies published up to September 30, 2023. The selection criteria were based on the Patients Interventions Comparisons Outcomes (PICOS) framework, focussing on studies involving ER+ BC patients treated with CDK4/6 inhibitors in combination with endocrine therapy. Both retrospective and prospective studies were included involving adult patients treated with standard doses of CDK4/6 inhibitors for approved indications.

The systematic review included 33 retrospective studies and one phase 2 study, encompassing 7,767 patients. Analysis revealed significant improvements in both OS (hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.61-0.93; P < .01) and PFS (HR = 0.87, 95% CI: 0.76-0.98; P = .02) among patients who underwent dosage reduction. The data exhibited low heterogeneity across studies, strengthening the reliability of our findings.

Our research provides valuable insights into the dosage optimisation of CDK4/6 inhibitors and its impact on patient outcomes. The findings suggest that when clinically indicated, dose reductions do not compromise treatment efficacy and may even improve survival outcomes. These results offer a promising direction for future clinical practices and research in oncology, particularly in personalising treatment approaches for patients with ER+ advanced BC.