Extreme responses to immune checkpoint blockade following bipolar androgen therapy and enzalutamide in patients with metastatic castration resistant prostate cancer

Mark C. Markowski, Eugene Shenderov, Mario A. Eisenberger, Sushant Kachhap, Drew M. Pardoll, Samuel R. Denmeade, Emmanuel S. Antonarakis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Immune checkpoint inhibition has been shown to have limited efficacy in patients with metastatic prostate cancer. Prostate cancers that harbor certain homologous recombination (HR) DNA repair gene mutations, inactivating CDK12 mutations or have underlying mismatch repair deficiency may be effectively treated with immunotherapy. Combination therapy may improve clinical response rates to immune checkpoint blockade. We observed profound prostate-specific antigen (PSA) and/or objective responses to immune checkpoint blockade following prior treatment with bipolar androgen therapy (BAT) and enzalutamide. Methods: We report three cases of patients with metastatic castration resistant prostate cancer (mCRPC) undergoing therapy with anti-PD-1 inhibitors. All patients underwent both somatic molecular testing and germline genetic testing. Results: Two of the three patients with mCRPC harbored an inactivating mutation in an HR DNA repair gene (BRCA2, ATM). No patient demonstrated mismatch repair deficiency, nor were CDK12 alterations present. All three patients had been treated with BAT and enzalutamide before immune checkpoint blockade, a paradoxical approach for the treatment of mCRPC developed by our group. Conclusions: These cases of mCRPC suggest that immune checkpoint blockade may have therapeutic potential in patients with prostate cancer, especially following immune activation (“priming”) using BAT and enzalutamide.

Original languageEnglish (US)
Pages (from-to)407-411
Number of pages5
JournalProstate
Volume80
Issue number5
DOIs
StatePublished - Apr 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins NIH grants P30 CA006973 and PCF Young Investigator and Challenge Awards. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Funding Information:
This study was supported by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins NIH grants P30 CA006973 and PCF Young Investigator and Challenge Awards. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Publisher Copyright:
© 2020 Wiley Periodicals, Inc.

Keywords

  • DNA repair
  • immunotherapy
  • prostate cancer
  • testosterone

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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