Overall Survival With Palbociclib and Aromatase Inhibitor Versus Aromatase Inhibitor Alone in Older Patients With HR+/HER2- Metastatic Breast Cancer

Abstract

Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the current standard of care for first-line (1L) treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). To investigate the effectiveness of palbociclib, the first-in-class CDK4/6i, plus an aromatase inhibitor (AI) in older patients, we compared overall survival (OS) in a Medicare population treated with 1L palbociclib + AI versus an AI alone.

Methods: Patients aged ≥ 65 years who were diagnosed with de novo HR+/HER2- mBC from 2015 to 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER)-linked Medicare database and were eligible if they initiated 1L palbociclib + AI or an AI alone. The primary endpoint was OS. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance baseline patient characteristics.

Results: Of 779 eligible patients, 296 received palbociclib + AI and 483 received AI alone as 1L treatment. After sIPTW, the median follow-up was 23.1 months with palbociclib + AI and 18.2 months with AI alone. Adjusted median OS was longer with palbociclib + AI versus AI alone (sIPTW: 37.6 vs. 25.5 months, HR = 0.73 [95% CI, 0.59-0.91]). In multivariable Cox proportional hazards regression, patients treated with palbociclib + AI versus AI alone had a 39% lower risk of death (HR = 0.61 [95% CI, 0.48-0.77]).

Conclusion: In routine US clinical practice, palbociclib + AI was associated with significantly prolonged OS versus AI alone in 1L treatment of patients aged ≥ 65 years with de novo HR+/HER2- mBC, adding to the growing body of evidence on the survival benefit of palbociclib + AI in this patient population.

Trial registration: ClinicalTrials.gov identifier: NCT06086340.

Keywords: CDK4/6 inhibitor; HR+/HER2– metastatic breast cancer; SEER; older adults; overall survival; palbociclib; real‐world evidence.

FIGURE 1

Patient selection flowchart.^a AI = aromatase inhibitor, CDK4/6i = cyclin‐dependent kinases 4 and 6 inhibitor, ET = endocrine therapy, HMO = health maintenance organization, HR+/HER2– = hormone receptor–positive and human epidermal growth factor receptor 2–negative, mBC = metastatic breast cancer. ^aTo ensure complete 1L therapy and healthcare encounter data, patients were required to maintain continuous enrollment in Medicare Parts A (inpatient care, hospital stays, care in a skilled nursing facility, hospice care, and some home health care), B (select healthcare provider [HCP] services, outpatient care, medical supplies, and preventative services), and D (prescription drugs) [40], with no HMO participation from the date of diagnosis until the index date and for ≥ 6 months before the index date. Patients were excluded if their mBC diagnosis was first recorded in a death certificate or at the time of autopsy.

FIGURE 2

KM analysis of overall survival. (A) Unadjusted analysis. (B) sIPTW analysis^a (Primary analysis). (C) PSM analysis. AI = aromatase inhibitor, CI = confidence interval, KM = Kaplan–Meier, OS = overall survival, PSM = propensity score matching; sIPTW = stabilized inverse probability of treatment weighting. ^aIn the sIPTW analysis, there was a sign of potential violation of the proportional hazard assumption for the treatment type: the Schoenfeld residuals test was significant; however, an interaction of treatment type with the log of time was found to be not significant.

FIGURE 3

Forest plot of sIPTW‐adjusted overall survival by subgroups. AI = aromatase inhibitor, CI = confidence interval, HR = hazard ratio, mBC = metastatic breast cancer, NCI = National Cancer Institute, sIPTW = stabilized inverse probability of treatment weighting.