Palbociclib plus endocrine therapy significantly enhances overall survival of HR+/HER2- metastatic breast cancer patients compared to endocrine therapy alone in the second-line setting: A large institutional study

Abstract

Cyclin-dependent-kinase-4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer (BC). The Breast Medical Oncology database at MD Anderson Cancer Center (MDACC) was analyzed to assess effectiveness of the CDK4/6i palbociclib plus ET compared to ET alone. From a total of 5402 advanced HR+ HER2- BC patients referred to MDACC between 1997 and 2020, we identified eligible patients who received palbociclib in combination with first-line (n = 778) and second-line (n = 410) ET. We further identified "control" patients who received ET alone in the first-line (n = 2452) and second-line (n = 1183) settings. Propensity score matching analysis was conducted to balance baseline demographic and clinical characteristics between palbociclib and control cohorts to assess the effect of palbociclib treatment on progression-free survival (PFS) and overall survival (OS). For propensity-matched-cohort in the first-line setting (n = 708), palbociclib group had significantly longer median PFS (17.4 vs 11.1 months; P < .0001) compared to controls. Median OS (44.3 vs 40.2 months) did not show a statistically significant benefit in the first line setting. However, in the second-line setting, with 380 propensity-matched-cohort, the palbociclib group had significantly longer PFS (10 vs 5 months, P < .0001) as well as OS (33 vs 24 months; P < .022), compared to controls. We conclude that in this single center analysis of a large cohort of metastatic HR+ HER2- BC patients, palbociclib in combination with ET was associated with improved PFS in both first-line and second-line settings and OS in the second-line setting compared to ET alone cohort.

Keywords: CDK4/6 inhibitors; Propensity matching; aromatase inhibitors; endocrine therapy; fulvestrant; hormone receptor; metastatic breast cancer; overall survival; progression-free survival.

[Figure 1]

STROBE Diagram

[Figure 2] –

Absolute standardized differences (ASD, probability) in observed covariates between ET alone and palbociclib + ET in the first-line (A) and second-line (B) settings (based on race, age, estrogen or progesterone receptor, neoadjuvant chemotherapy use, lymphovascular invasion, clinical tumor, nodal and metastasis categories, and adjuvant chemotherapy use); the covariates with postmatch (green dots) absolute standardized differences below 0.1 are considered as successfully balanced.

[Figure 3]

PFS curves and the hazard estimates over time according to treatments. The survival curves are shown up to maximum follow-up time of the CDK4/6 inhibitor treatment groups. (A) PFS1 survival curves and the shaded 95% CIs for the first-line setting. (B) PFS2 survival curves and the shaded 95% CIs for the second-line setting. (C) PFS1 hazard ratio curves are presented with shaded 95% CIs for first-line treatment cohort. (D) PFS2 hazard ratio curves are presented with shaded 95% CIs for the second-line treatment cohorts.

[Figure 4]

Overall survival curves and hazard estimates over time according to treatments. The survival curves are shown up to maximum follow-up time of the palbociclib treatment groups. (A) Survival curves and the shaded 95% CIs for the first-line setting. (B) Survival curves and the shaded 95% CIs for the second-line setting. (C) Hazard curves with shaded 95% CIs for the first-line setting. (D) Hazard curves with shaded 95% CIs for the second-line setting.

[Figure 5]

A: Hazard ratios (HRs) with shaded 95% confidence intervals for PFS and OS according to baseline characteristics in the first-line treatment analysis. HRs for subgroups with small sample sizes are not reported. B: HRs with shaded 95% confidence intervals for PFS and OS according to baseline characteristics in the second-line analysis. HRs for subgroups with small sample sizes are not reported.