Skip to main content

Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.

Publication ,  Journal Article
Tsuji, J; Li, T; Grinshpun, A; Coorens, T; Russo, D; Anderson, L; Rees, R; Nardone, A; Patterson, C; Lennon, NJ; Cibulskis, C; Leshchiner, I ...
Published in: Clinical cancer research : an official journal of the American Association for Cancer Research
December 2022

Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated.We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2- advanced breast cancer who progressed on prior ET (N = 36; NCT02448771).The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0-7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5-13; P = 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES; N = 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment.The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2- breast cancer. These results merit continued investigation of bazedoxifene in breast cancer.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

December 2022

Volume

28

Issue

23

Start / End Page

5066 / 5078

Related Subject Headings

  • Treatment Outcome
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Liquid Biopsy
  • Humans
  • Female
  • Exome Sequencing
  • Breast Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tsuji, J., Li, T., Grinshpun, A., Coorens, T., Russo, D., Anderson, L., … Jeselsohn, R. (2022). Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 28(23), 5066–5078. https://doi.org/10.1158/1078-0432.ccr-22-2305
Tsuji, Junko, Tianyu Li, Albert Grinshpun, Tim Coorens, Douglas Russo, Leilani Anderson, Rebecca Rees, et al. “Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 28, no. 23 (December 2022): 5066–78. https://doi.org/10.1158/1078-0432.ccr-22-2305.
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, et al. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Dec;28(23):5066–78.
Tsuji, Junko, et al. “Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 28, no. 23, Dec. 2022, pp. 5066–78. Epmc, doi:10.1158/1078-0432.ccr-22-2305.
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, McDonnell DP, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Dec;28(23):5066–5078.

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

December 2022

Volume

28

Issue

23

Start / End Page

5066 / 5078

Related Subject Headings

  • Treatment Outcome
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Liquid Biopsy
  • Humans
  • Female
  • Exome Sequencing
  • Breast Neoplasms