Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer
Open accessAbstract
BACKGROUND: Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. METHODS: In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. RESULTS: As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. CONCLUSIONS: Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).
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Multiple phase 3 clinical trials have demonstrated the benefit of AR-targeted therapies on patient survival.
“Multiple phase 3 clinical trials have demonstrated the benefit of AR-targeted therapies on patient survival9–18.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [17]
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Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
Scher, H. I., Fizazi, K., Saad, F., Taplin, M.-E., Sternberg, C. N., Miller, K., de Wit, R., Mulders, P., Chi, K. N., Shore, N. D., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1207506 · Cited by 4,586 · see citing works
Self-citationEnzalutamide in Metastatic Prostate Cancer before Chemotherapy
Beer, T. M., Armstrong, A. J., Rathkopf, D. E., Loriot, Y., Sternberg, C. N., Higano, C. S., Iversen, P., Bhattacharya, S., Carles, J., Chowdhury, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1405095 · Cited by 3,028 · see citing works
Self-citationApalutamide Treatment and Metastasis-free Survival in Prostate Cancer
Smith, M. R., Saad, F., Chowdhury, S., Oudard, S., Hadaschik, B. A., Graff, J. N., Olmos, D., Mainwaring, P. N., Lee, J. Y., Uemura, H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1715546 · Cited by 1,344 · see citing works
Self-citationArmstrong, A. J., Szmulewitz, R. Z., Petrylak, D. P., Holzbeierlein, J. M., Villers, A. A., Azad, A., Alcaraz, A., Alekseev, B. Y., Iguchi, T., Shore, N. D., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.00799 · Cited by 1,219 · see citing works
Self-citationEnzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer
Hussain, M., Fizazi, K. S., Fred Saad, C., Rathenborg, P., Shore, N. D., Ferreira, U., Ivashchenko, P., Demirhan, E., Modelska, K., Phung, D., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1800536 · Cited by 1,041 · see citing works
Self-citationDarolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer
Fizazi, K., Shore, N., Tammela, T. L., Ulys, A., Vjaters, E., Polyakov, S., Jievaltas, M., Luz, M., Alekseev, B., Kuss, I., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1815671 · Cited by 930 · see citing works
Self-citationSmith, M. R., Kabbinavar, F. F., Fred Saad, C., Hussain, A., Gittelman, M., Bilhartz, D. L., Wynne, C., Murray, R. N., Zinner, N. R., Schulman, C., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.529 · Cited by 496 · see citing works
Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer
Xie, W., Regan, M. M., Buyse, M. E., Halabi, S., Kantoff, P. W., Sartor, O. A., Soule, H. R., Clarke, N. W., Collette, L., Dignam, J. J., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.73.9987 · Cited by 437 · see citing works
Self-citationGillessen, S., Attard, G., Beer, T. M., Beltran, H., Bjartell, A. S., Bossi, A., Briganti, A., Bristow, R. G., Chi, K. N., Clarke, N. W., et al. (2020) · European Urology · doi:10.1016/j.eururo.2020.01.012 · Cited by 394 · see citing works
Self-citationEnzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial
Penson, D. F., Armstrong, A. J., Concepcion, R. S., Agarwal, N., Olsson, C. A., Karsh, L. I., Dunshee, C. J., Wang, F., Wu, K. K., Krivoshik, A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.9285 · Cited by 323 · see citing works
Self-citationShore, N. D., Chowdhury, S., Villers, A. A., Klotz, L. H., Siemens, D. R., Phung, D., van Os, S., Hasabou, N., Wang, F., Bhattacharya, S., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00518-5 · Cited by 283 · see citing works
Self-citationFendler, W. P., Weber, M., Iravani, A., Hofman, M. S., Calais, J., Czernin, J., Ilhan, H., Saad, F., Small, E. J., Smith, M. R., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1050 · Cited by 266 · see citing works
Managing Nonmetastatic Castration-resistant Prostate Cancer
Mateo, J., Fizazi, K. S., Gillessen, S., et al. (2018) · European Urology · doi:10.1016/j.eururo.2018.07.035 · Cited by 161 · see citing works
Self-citationApalutamide and overall survival in non-metastatic castration-resistant prostate cancer
Small, E. J., Fred Saad, C., Chowdhury, S., Oudard, S. M., Hadaschik, B. A., Graff, J. N., Olmos, D., Mainwaring, P. N., Lee, J. Y., Uemura, H., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz397 · Cited by 144 · see citing works
TOMBAL, B. F., Fred Saad, C., Penson, D. F., Hussain, M., Sternberg, C. N., Morlock, R., Ramaswamy, K., Ivanescu, C., & Attard, G. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30898-2 · Cited by 107 · see citing works
Self-citationAfshar, M., Evison, F., James, N. D., & Patel, P. (2015) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2015.05.003 · Cited by 36 · see citing works
Jenkins, V. A., Solis‐Trapala, I., Payne, H. A., Mason, M. D., Fallowfield, L. J., May, S. F., Matthews, L., & Catt, S. (2018) · Clinical Oncology · doi:10.1016/j.clon.2018.11.001 · Cited by 20 · see citing works
A Retrospective Claims Analysis of Advanced Prostate Cancer Costs and Resource Use
Appukkuttan, S., Tangirala, K., Babajanyan, S., et al. (2019) · PharmacoEconomics - Open · doi:10.1007/s41669-019-00185-8 · Cited by 18 · see citing works
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Research works printed but not linked: 1
- Scher HI, Fizazi K, Saad F, et al. In- creased survival with enzalutamide in pros- tate cancer after chemotherapy. N Engl J Med 2012; 367: 1187-97.
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Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., McEachern, D., Wang, Y., Metwally, H., Wang, L., Matvekas, A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00882 · Cited by 170 · see citing works
Fizazi, K., & Gillessen, S. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.02.015 · Cited by 119 · see citing works
Self-citationJoshua, A. M., Armstrong, A., Crumbaker, M., Scher, H. I., de Bono, J., Tombal, B., Hussain, M., Sternberg, C. N., Gillessen, S., Carles, J., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.04.005 · Cited by 28 · see citing works
Self-citationLi, H., Melnyk, J. E., Fu, B. X. H., Shrestha, R., Zhang, M., Sjöström, M., Feng, S., Anderson, J. A., Han, W., Chesner, L. N., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02388-8 · Cited by 10 · see citing works
- Authors
- Sternberg, C. N., Fizazi, K., Saad, F., Shore, N. D., De Giorgi, U., Penson, D. F., Ferreira, U., Efstathiou, E., Madziarska, K., Kolinsky, M. P., Cubero, D. I. G., Noerby, B., Zohren, F., Lin, X., Modelska, K., Sugg, J., Steinberg, J., & Hussain, M.
- Affiliations
- University of Alberta (CA)
- From the Englander Institute for Precision Medicine, Weill Cornell Medicine, New York (C.N.S.); the University of Paris Saclay, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.), and Cross Cancer Institute, University of Alberta, Edmonton (M.P.K.) — both in Canada; the Carolina Urologic Research Center, Myrtle Beach, SC (N.D.S.); Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy (U.D.); Vanderbilt University, Nashville ...
- The University of Texas MD Anderson Cancer Center (US)
- Northwestern University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-06-04
- Volume
- 382
- Issue
- 23
- Pages
- 2197-2206
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3031020438
- Cited by
- 428
- References
- 18
- Citations by year
- 2026: 36 · 2025: 47 · 2024: 73 · 2023: 62 · 2022: 82 · 2021: 89 · 2020: 36 · 2019: 1 · 2014: 1
- FWCI
- 37.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- AIRUS (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Pfizer Inc. and Astellas Pharma
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- enzalutamide, non-metastatic castration-resistant prostate cancer, androgen deprivation therapy, overall survival, prostate-specific antigen, metastasis-free survival, adverse events, fatigue, PROSPER trial, androgen receptor antagonists, prostate cancer treatment outcomes, mortality risk reduction, PSA doubling time, drug safety profile, group sequential analysis
- MeSH terms
- Adenocarcinoma, Aged, Androgen Antagonists, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Double-Blind Method, Humans, Kallikreins, Male, Middle Aged, Nitriles, Phenylthiohydantoin, Placebos, Survival Analysis, Prostate-Specific Antigen, Kaplan-Meier Estimate, Prostatic Neoplasms, Castration-Resistant
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