Michael S Humeniuk1, Rajan T Gupta2,3, Patrick Healy4, Megan McNamara1, Sundhar Ramalingam1, Michael Harrison1,3, Daniel George3,5, Tian Zhang1, Yuan Wu4, Andrew J Armstrong6,7. 1. Duke University Department of Medicine, Durham, NC, 27710, USA. 2. Duke University Department of Radiology, Durham, NC, 27710, USA. 3. Duke Cancer Institute, Durham, NC, 27710, USA. 4. Duke University Department of Biostatistics and Bioinformatics, Durham, NC, 27710, USA. 5. Departments of Medicine and Surgery, Pharmacology and Cancer Biology, Divisions of Medical Oncology and Urology, Durham, NC, 27710, USA. 6. Duke Cancer Institute, Durham, NC, 27710, USA. Andrew.armstrong@duke.edu. 7. Departments of Medicine and Surgery, Pharmacology and Cancer Biology, Divisions of Medical Oncology and Urology, Durham, NC, 27710, USA. Andrew.armstrong@duke.edu.
Abstract
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.
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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