In a U.S. Food and Drug Administration (FDA) pooled analysis reported in the Journal of Clinical Oncology, Howie et al found that progression-free survival and benefit were similar for older vs younger postmenopausal women treated with combined cyclin-dependent kinase 4/6 (CDK4/6) plus aromatase inhibitor therapy vs aromatase inhibitor therapy alone for hormone receptor–positive, HER2-negative metastatic breast cancer. Older women had higher rates of toxicity.

The study involved data for 1,827 patients from three randomized trials evaluating the combination of a CDK4/6 inhibitor and an aromatase inhibitor for the initial treatment of postmenopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer. The primary outcome measure was progression-free survival.

Progression-Free Survival

On multivariate analysis, among 198 women aged ≥ 75 years old, median progression-free survival was 31.1 months among those receiving the combination of a CDK4/6 inhibitor and an aromatase inhibitor vs 13.7 months among those receiving an aromatase inhibitor alone (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.31–0.76). Among patients aged < 75 years old, median progression-free survival was 27.6 months among those receiving combination treatment vs 14.9 months among those receiving an aromatase inhibitor alone (HR = 0.56, 95% CI = 0.49–0.64).

The hazard ratio for progression-free survival for age ≥ 75 years old vs < 75 years old was 0.93 (95% CI = 0.76–1.13) among women receiving combination therapy and 1.05 (95% CI = 0.85–1.30) among those receiving an aromatase inhibitor alone.

Adverse Events

Among patients receiving CDK4/6 inhibitor plus aromatase inhibitor treatment, grade 3 or 4 adverse events occurred in 88.8% of those aged ≥ 75 years old and in 73.4% of those aged < 75 years old. Adverse events led to dose interruption or reduction in 81.6% vs 71.1% of patients and to treatment discontinuation in 32.0% vs 12.1%. Serious adverse events occurred in 46.4% vs 22.8%. Irrespective of receipt of combined therapy or an aromatase inhibitor alone, patients aged ≥ 75 years reported more rapid deterioration in EQ-5D mobility, self-care, and ability to perform usual activities domains vs younger patients.

The investigators concluded, “There was similar efficacy with a CDK4/6 inhibitor in combination with an aromatase inhibitor compared with an aromatase inhibitor alone for first-line treatment of [hormone receptor]-positive, HER2-negative metastatic breast cancer in older women compared with younger patients. Patients older than age 75 years experienced higher rates of toxicity, dose modifications, and a decrease from baseline in quality-of-life measures.”

Harpreet Singh, MD, of the FDA's Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.