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Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation.

Publication ,  Journal Article
Berger, BT; Labriola, MK; Antonarakis, ES; Armstrong, AJ
Published in: BMJ Case Rep
January 18, 2023

We present the case of a patient with germline CHEK2-mutated metastatic castration-resistant prostate cancer (mCRPC) who responded to bipolar androgen therapy (BAT) combined with pembrolizumab after progressing through multiple lines of therapy. The patient was diagnosed in his 40s following an elevated screening prostate-specific antigen and biopsy. Over the course of 20 years, he progressed through nearly all standard therapies including androgen deprivation, combined androgen blockade, traditional chemotherapy, targeted therapies and experimental agents. He was ultimately treated with BAT, whereby the patient's cycle was between low (castrate) and high (supraphysiological) testosterone levels. This counterintuitive approach resulted in a marked response to BAT plus pembrolizumab consolidation lasting 13 months. His underlying germline mutation in CHEK2, an important mediator of DNA repair, may have sensitised the cancer cells to the DNA damage caused by BAT. Single case report outcomes should not be used as evidence of efficacy for treatment regimes. Our case supports further investigation into BAT plus immunotherapy for patients with DNA repair-deficient mCRPC.

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Published In

BMJ Case Rep

DOI

EISSN

1757-790X

Publication Date

January 18, 2023

Volume

16

Issue

1

Location

England

Related Subject Headings

  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Programmed Cell Death 1 Receptor
  • Male
  • Humans
  • Germ-Line Mutation
  • Germ Cells
  • Checkpoint Kinase 2
  • Androgens
  • Androgen Antagonists
 

Citation

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Berger, B. T., Labriola, M. K., Antonarakis, E. S., & Armstrong, A. J. (2023). Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation. BMJ Case Rep, 16(1). https://doi.org/10.1136/bcr-2022-251320
Berger, Benjamin T., Matthew K. Labriola, Emmanuel S. Antonarakis, and Andrew J. Armstrong. “Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation.BMJ Case Rep 16, no. 1 (January 18, 2023). https://doi.org/10.1136/bcr-2022-251320.
Berger, Benjamin T., et al. “Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation.BMJ Case Rep, vol. 16, no. 1, Jan. 2023. Pubmed, doi:10.1136/bcr-2022-251320.

Published In

BMJ Case Rep

DOI

EISSN

1757-790X

Publication Date

January 18, 2023

Volume

16

Issue

1

Location

England

Related Subject Headings

  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Programmed Cell Death 1 Receptor
  • Male
  • Humans
  • Germ-Line Mutation
  • Germ Cells
  • Checkpoint Kinase 2
  • Androgens
  • Androgen Antagonists