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Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study

Jacob A. Gordon, Carlo Buonerba, Gregory Pond, Daniel Crona, Silke Gillessen, Giuseppe Lucarelli, Sabrina Rossetti, Tanya Dorff, Salvatore Artale, Jennifer A. Locke, Davide Bosso, Matthew Ivan Milowsky, Mira Sofie Witek, Michele Battaglia, Sandro Pignata, Cyrus Cherhroudi, Michael E. Cox, Pietro De Placido, Dario Ribera, Aurelius Omlin, Gaetano Buonocore, Kim Chi, Christian Kollmannsberger, Daniel Khalaf, Gaetano Facchini, Guru Sonpavde, Sabino De Placido, Bernhard J. Eigl and Giuseppe Di Lorenzo _

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Oncotarget. 2018; 9:19861-19873. https://doi.org/10.18632/oncotarget.24888

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Abstract

Jacob A. Gordon1,*, Carlo Buonerba2,3,*, Gregory Pond4, Daniel Crona5, Silke Gillessen6, Giuseppe Lucarelli7, Sabrina Rossetti8, Tanya Dorff9, Salvatore Artale10, Jennifer A. Locke1, Davide Bosso2, Matthew Ivan Milowsky5, Mira Sofie Witek6, Michele Battaglia7, Sandro Pignata11, Cyrus Cherhroudi12, Michael E. Cox1, Pietro De Placido2, Dario Ribera2, Aurelius Omlin6, Gaetano Buonocore13, Kim Chi14, Christian Kollmannsberger14, Daniel Khalaf14, Gaetano Facchini8, Guru Sonpavde15, Sabino De Placido2, Bernhard J. Eigl14,# and Giuseppe Di Lorenzo2,#

1Vancouver Prostate Center, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada

2Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

3Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy

4McMaster University, Hamilton, Ontario, Canada

5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA

6Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

7Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy

8S.S.D Oncologia Clinica Sperimentale Uro-Andrologica, Dipartimento Corp-S Assistenziale dei Percorsi Oncologici Uro-Genitale, Istituto Nazionale Tumori Fondazione G. Pascale-IRCCS, Naples, Italy

9University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California, USA

10Oncology Department, Ospedale di Gallarate ASST Valle Olona, Gallarate, Italy

11Division of Medical Oncology, Department of Uro-Gynecologi cal Oncology, Istituto Nazionale Tumori Fondazione G. Pascale-IRCCS, Naples, Italy

12Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

13Hospital Directorate, Azienda Ospedaliera Universitaria Federico II of Naples, Naples, Italy

14BC Cancer, Vancouver, British Columbia, Canada

15Genitourinary Oncology Section, Dana Farber Cancer Institute, Boston, Massachusetts, USA

*These two authors equally contributed to this work

#These two authors share equal senior authorship

Correspondence to:

Giuseppe Di Lorenzo, email: [email protected]

Keywords: prostate cancer; abiraterone; enzalutamide; statins

Received: February 01, 2018     Accepted: February 27, 2018     Published: April 13, 2018

ABSTRACT

Background: Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide.

Materials and methods: This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated. The associations of statins with early (≤12 weeks) prostate-specific antigen (PSA) declines (> 30%), cancer-specific survival and overall survival (OS) were evaluated after controlling for known prognostic factors.

Results: Five hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months (95% CI = 18.3–23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4–14.6) for patients who did not receive statins (P < 0.001). After adjusting for age, alkaline phosphatase, PSA, neutrophil-to-lymphocytes ratio, Charlson comorbidity score, Gleason score, visceral disease, hemoglobin, opiate use and abiraterone versus enzalutamide treatment, the use of statin therapy was associated with a 53% reduction in the overall risk of death (hazard ratio [HR] = 0.47; 95% CI = 0.35–0.63; P < 0.001). Statin use was also associated with a 63% increased odds of a > 30% PSA decline within the first 12 weeks of treatment (OR = 1.63; 95% CI = 1.03–2.60; P = 0.039).

Conclusions: In this retrospective cohort, statin use was significantly associated with both prolonged OS and cancer-specific survival and increased early > 30% PSA declines. Prospective validation is warranted.


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