Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study

Eur J Cancer. 2022 Jun:168:12-24. doi: 10.1016/j.ejca.2022.03.006. Epub 2022 Apr 13.

Abstract

Background: An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis.

Methods: Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death).

Results: OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed.

Conclusions: Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.

Trial registration: NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT).

Keywords: CDK4/6 inhibitor; Capecitabine; Endocrine therapy; HER2–negative; Hormone receptor-positive metastatic breast cancer; Overall survival; Palbociclib.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms* / pathology
  • Capecitabine / therapeutic use
  • Female
  • Fulvestrant / therapeutic use
  • Humans
  • Piperazines
  • Postmenopause
  • Pyridines
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism

Substances

  • Aromatase Inhibitors
  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Fulvestrant
  • Capecitabine
  • Receptor, ErbB-2
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT02028507
  • EudraCT/2013-003170-27