TY - JOUR
T1 - Platinum sensitivity in metastatic prostate cancer
T2 - Does histology matter?
AU - Humeniuk, Michael S.
AU - Gupta, Rajan T.
AU - Healy, Patrick
AU - McNamara, Megan
AU - Ramalingam, Sundhar
AU - Harrison, Michael
AU - George, Daniel
AU - Zhang, Tian
AU - Wu, Yuan
AU - Armstrong, Andrew J.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. Methods: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent. Data surrounding clinical features, histology, imaging, safety, and neuroendocrine transformation were collected. Scans were re-reviewed using RECIST v1.1 criteria to estimate responses as well as calculate radiographic progression-free survival (rPFS). Results: A database search identified 73 men with mCRPC treated with cisplatin, carboplatin, or oxaliplatin. There were three men with primary NEPC and small cell prostate cancer, and 14 with a NEPC transformation. In the first-line setting, 10 (63%) men with NEPC had a partial response (PR) compared with 14 (29%) of the men with adenocarcinoma (p = 0.017), with a median rPFS of 5.1 mo (3.1-7.8) and 4.3 mo (3.0-5.2 mo), respectively. The median overall survival was 8.5 mo (6.4-20.1 mo) for men with NEPC compared to 10.0 mo (8.0-14.4) in men with adenocarcinoma. Prostate-specific antigen (PSA) declines meeting >30%, >50%, and >90% criteria from baseline were observed in 64/57/29% of NEPC patients (n = 14) treated with platinum chemotherapy vs. 48/30/14% of men with prostate adenocarcinoma (n = 50), respectively. Conclusions: This study suggests that NEPC histology enriches for platinum sensitivity, but that an important minority group (20-30%) of men with adenocarcinoma have a clinical benefit with platinum-based chemotherapy. Molecular predictors, such as germline or somatic mutations in DNA repair enzymes, should be evaluated for platinum responsiveness.
AB - Background: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. Methods: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent. Data surrounding clinical features, histology, imaging, safety, and neuroendocrine transformation were collected. Scans were re-reviewed using RECIST v1.1 criteria to estimate responses as well as calculate radiographic progression-free survival (rPFS). Results: A database search identified 73 men with mCRPC treated with cisplatin, carboplatin, or oxaliplatin. There were three men with primary NEPC and small cell prostate cancer, and 14 with a NEPC transformation. In the first-line setting, 10 (63%) men with NEPC had a partial response (PR) compared with 14 (29%) of the men with adenocarcinoma (p = 0.017), with a median rPFS of 5.1 mo (3.1-7.8) and 4.3 mo (3.0-5.2 mo), respectively. The median overall survival was 8.5 mo (6.4-20.1 mo) for men with NEPC compared to 10.0 mo (8.0-14.4) in men with adenocarcinoma. Prostate-specific antigen (PSA) declines meeting >30%, >50%, and >90% criteria from baseline were observed in 64/57/29% of NEPC patients (n = 14) treated with platinum chemotherapy vs. 48/30/14% of men with prostate adenocarcinoma (n = 50), respectively. Conclusions: This study suggests that NEPC histology enriches for platinum sensitivity, but that an important minority group (20-30%) of men with adenocarcinoma have a clinical benefit with platinum-based chemotherapy. Molecular predictors, such as germline or somatic mutations in DNA repair enzymes, should be evaluated for platinum responsiveness.
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U2 - 10.1038/s41391-017-0017-6
DO - 10.1038/s41391-017-0017-6
M3 - Article
C2 - 29230006
AN - SCOPUS:85037686630
SN - 1365-7852
VL - 21
SP - 92
EP - 99
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 1
ER -