Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up

Breast Cancer Res Treat. 2019 Apr;174(3):719-729. doi: 10.1007/s10549-018-05125-4. Epub 2019 Jan 10.

Abstract

Purpose: In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up.

Methods: In this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).

Results: After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.

Conclusions: With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.

Keywords: Breast cancer; Cyclin-dependent kinase inhibitor; ER+; HER2−; Letrozole; Palbociclib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Letrozole / administration & dosage*
  • Letrozole / adverse effects
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Postmenopause / psychology
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Quality of Life / psychology
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Treatment Outcome

Substances

  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Letrozole
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT01740427