Efficacy of Palbociclib Combinations in Hormone Receptor-Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment

Clin Breast Cancer. 2018 Dec;18(6):e1401-e1405. doi: 10.1016/j.clbc.2018.04.015. Epub 2018 Apr 28.

Abstract

Purpose: Outcome data on hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2-) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+HER2- MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+HER2- MBC with prior exposure to everolimus while receiving palbociclib-based therapy.

Patients and methods: A retrospective, single-institute review was conducted of HR+HER2- MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks.

Results: Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively.

Conclusion: There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.

Keywords: CDK 4/6 inhibitor; Endocrine therapy; Resistance to endocrine therapy; Sequential endocrine therapy; mTOR inhibitor.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Everolimus / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Piperazines / administration & dosage
  • Prognosis
  • Pyridines / administration & dosage
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Everolimus
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib