Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice

Breast Cancer Res. 2021 Mar 24;23(1):37. doi: 10.1186/s13058-021-01409-8.

Abstract

Background: Findings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA.

Patients and methods: This was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed.

Results: After sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53-0.82; P = 0.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results.

Conclusions: In this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.

Trial registration: Clinicaltrials.gov; NCT04176354.

Keywords: Comparative effectiveness; HR+/HER2−; Letrozole; Metastatic breast cancer; Palbociclib; Real-world data.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Letrozole / therapeutic use*
  • Middle Aged
  • Piperazines / therapeutic use*
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / therapeutic use*
  • Receptor, ErbB-2 / deficiency
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Survival Rate

Substances

  • Aromatase Inhibitors
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Letrozole
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT04176354