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Extreme responses to immune checkpoint blockade following bipolar androgen therapy and enzalutamide in patients with metastatic castration resistant prostate cancer
Author(s) -
Markowski Mark C.,
Shenderov Eugene,
Eisenberger Mario A.,
Kachhap Sushant,
Pardoll Drew M.,
Denmeade Samuel R.,
Antonarakis Emmanuel S.
Publication year - 2020
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23955
Subject(s) - enzalutamide , prostate cancer , medicine , blockade , immune checkpoint , immunotherapy , oncology , androgen deprivation therapy , immune system , cancer , cancer research , androgen receptor , immunology , receptor
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.