105 Real-World Overall Survival With Palbociclib Plus an Aromatase Inhibitor (AI) in Overweight/Obese Patients With HR+/HER2− Metastatic Breast Cancer (MBC)

Background

A CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy has been the standard of care (SOC) as first-line treatment for hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer for the past decade. Palbociclib, the first CDK4/6i approved, received accelerated US approval in 2015 for HR+/HER2− metastatic breast cancer based on its demonstrated efficacy and safety profile. An increasing number of real-world studies have shown that first-line palbociclib plus endocrine therapy significantly improves progression-free survival, tumor response, and overall survival (OS) compared with endocrine therapy alone across diverse HR+/HER2− metastatic breast cancer populations. Overweight and obesity are common conditions associated with an increased risk of breast cancer and can influence cancer treatment outcomes. However, little is known about the effectiveness of CDK4/6i plus endocrine therapy, specifically in overweight/obese patients with HR+/HER2− metastatic breast cancer in routine US clinical practice.

Methods

This was a retrospective analysis of deidentified longitudinal data from the Flatiron Health Research Database. Patients were included if they were overweight or obese (body mass index ≥25 kg/m²), had HR+/HER2− metastatic breast cancer, and initiated first-line palbociclib plus aromatase inhibitor or aromatase inhibitor between February 2015 to July 2024. OS was defined as the number of months from start of palbociclib plus aromatase inhibitor or aromatase inhibitor alone to death. Date of death was a consensus mortality end point based on electric health records, Social Security Death Index, and obituary data, validated against the National Death Index. Patients were retrospectively followed until death, last medical activity, or January 2025 (data cut-off), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance patient characteristics. Cox proportional hazards models were used to estimate the relative effectiveness of palbociclib plus aromatase inhibitor or aromatase inhibitor alone.

Results

A total of 8076 patients were eligible for the analysis, including 5009 (62.0%) treated with palbociclib plus aromatase inhibitor and 3067 (38.0%) treated with aromatase inhibitor alone (Table). Compared with aromatase inhibitor-alone patients, those treated with palbociclib plus aromatase inhibitor were younger and more likely to have 2 or more metastatic sites and lung/liver involvement but less likely to have ECOG score 2 or higher. After sIPTW, patient characteristics were generally balanced. Unadjusted median OS was 51.4 months (95% CI; 49.3-53.4) with palbociclib plus aromatase inhibitor and 41.1 months (95% CI, 38.9-43.3) months with AI (hazard ratio [HR], 0.75; 95% CI, 0.71-0.80); P <.0001). After sIPTW, median OS was 50.7 months (95% CI, 48.7-53.1) with palbociclib plus aromatase inhibitor and 42.4 months (95% CI, 39.8-44.7) with aromatase inhibitor (HR, 0.79; 95% CI, 0.74-0.85; P <.0001). Consistent results were observed with 1:1 propensity score matching as a sensitivity analysis. See Table for baseline patient characteristics and OS results.

Conclusions

Compared with aromatase inhibitor alone, palbociclib plus aromatase inhibitor is associated with improved OS in overweight/obese patients with HR+/HER2- metastatic breast cancer in US real-world setting, supporting first line palbociclib plus aromatase inhibitor as a SOC for overweight/obese patients with HR+/HER2- metastatic breast cancer.

Funding Source: Pfizer Inc.

Acknowledgment: Medical editorial support was provided by Dominique J. Verlaan, PhD, of Oxford PharmaGenesis Inc, Wilmington, DE, USA, with funding provided by Pfizer Inc, USA.