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

Benjamin T. Berger; Matthew K. Labriola; Emmanuel S. Antonarakis; Andrew J. Armstrong

doi:10.1136/bcr-2022-251320

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

Benjamin T. Berger
, Matthew K. Labriola
, Emmanuel S. Antonarakis
, Andrew J. Armstrong

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e251320
Journal	BMJ case reports
Volume	16
Issue number	1
DOIs	https://doi.org/10.1136/bcr-2022-251320
State	Published - Jan 18 2023

Bibliographical note

Funding Information:
We wish to thank the Duke University Internal Medicine Program and the Duke Clinical Research Institute for their support, the Duke University Medical Center Library for providing BMJ fellowship, and our patient for his selflessness and courage to share his story.

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cancer intervention
Oncology
Prostate
Prostate Cancer

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10.1136/bcr-2022-251320

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

abstract = "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.",

keywords = "Cancer intervention, Oncology, Prostate, Prostate Cancer",

author = "Berger, \{Benjamin T.\} and Labriola, \{Matthew K.\} and Antonarakis, \{Emmanuel S.\} and Armstrong, \{Andrew J.\}",

note = "Funding Information: We wish to thank the Duke University Internal Medicine Program and the Duke Clinical Research Institute for their support, the Duke University Medical Center Library for providing BMJ fellowship, and our patient for his selflessness and courage to share his story. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. ",

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AU - Berger, Benjamin T.

AU - Labriola, Matthew K.

AU - Antonarakis, Emmanuel S.

AU - Armstrong, Andrew J.

N1 - Funding Information: We wish to thank the Duke University Internal Medicine Program and the Duke Clinical Research Institute for their support, the Duke University Medical Center Library for providing BMJ fellowship, and our patient for his selflessness and courage to share his story. Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2023/1/18

Y1 - 2023/1/18

N2 - 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.

AB - 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.

KW - Cancer intervention

KW - Oncology

KW - Prostate

KW - Prostate Cancer

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ER -

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

Abstract

Bibliographical note

UN SDGs

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