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Platinum sensitivity in metastatic prostate cancer: does histology matter?

Prostate Cancer and Prostatic Diseases volume 21, pages 92–99 (2018)Cite this article

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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.

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Fig. 1
Fig. 2: Waterfall plots.
Fig. 3: Kaplan-Meier curves.

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Acknowledgments

This study was supported in part by the DCI P30 core grant P30 CA01423 for biostatistical core support.

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Authors and Affiliations

  1. Duke University Department of Medicine, Durham, NC, 27710, USA

    Michael S. Humeniuk, Megan McNamara, Sundhar Ramalingam, Michael Harrison & Tian Zhang

  2. Duke University Department of Radiology, Durham, NC, 27710, USA

    Rajan T. Gupta

  3. Duke Cancer Institute, Durham, NC, 27710, USA

    Rajan T. Gupta, Michael Harrison, Daniel George & Andrew J. Armstrong

  4. Duke University Department of Biostatistics and Bioinformatics, Durham, NC, 27710, USA

    Patrick Healy & Yuan Wu

  5. Departments of Medicine and Surgery, Pharmacology and Cancer Biology, Divisions of Medical Oncology and Urology, Durham, NC, 27710, USA

    Daniel George & Andrew J. Armstrong

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  1. Michael S. Humeniuk
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Corresponding author

Correspondence to Andrew J. Armstrong.

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Competing interest

A.J.A. reports research funding (to Duke) from Medivation/Astellas, Bayer, Dendreon, and Janssen, Active Biotech, sanofi aventis, Gilead, Novartis, and Pfizer, and consulting/speaking with Dendreon and Sanofi aventis, consulting with Medivation/Astellas and Janssen. M.R.H. reports research funding (to Duke) from Medivation/Astellas, Acerta, Bristol Myers Squibb, Exelixis, Janssen, and Genentech; and consulting/speaking with Dendreon, Genentech, Exelixis, and Sanofi Aventis. D.J.G. reports research support from Janssen, Acerta, Millennium, Celldex, consulting with Acceleron Pharma, Astellas/Medivation, BioPharm Communications; consulting/research support from Bristol Myers Squibb Co, Exelixis Inc, Genentech, Innocrin, Pfizer Inc; and consulting/speaking/research support from Bayer Healthcare Pharmaceuticals, Dendreon Corporation, Novartis, and Sanofi Aventis. T.Z. reports research support from Janssen, Acerta, and Pfizer. R.T.G. reports consulting with Bayer Pharma AG, Halyard Health and Invivo Corp. as well as speakers bureau with Bayer Pharma AG. M.McN. reports research funding (to Duke) from Medivation/Astellas, Janssen, and Bayer Healthcare Pharmaceuticals.

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Humeniuk, M.S., Gupta, R.T., Healy, P. et al. Platinum sensitivity in metastatic prostate cancer: does histology matter?. Prostate Cancer Prostatic Dis 21, 92–99 (2018). https://doi.org/10.1038/s41391-017-0017-6

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