Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer
Open accessAbstract
BACKGROUND: Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy. The primary end point was metastasis-free survival, with the presence of metastasis determined by independent central review of radiographic imaging every 16 weeks. RESULTS: In total, 1509 patients underwent randomization (955 to the darolutamide group and 554 to the placebo group). In the planned primary analysis, which was performed after 437 primary end-point events had occurred, the median metastasis-free survival was 40.4 months with darolutamide, as compared with 18.4 months with placebo (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P<0.001). Darolutamide was also associated with benefits with regard to all secondary end points, including overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event. The incidence of adverse events that occurred or worsened during the treatment period and had a frequency of 5% or more or were of grade 3 or higher was similar in the two groups; all such events except fatigue occurred in less than 10% of patients in either group. The percentage of patients who discontinued the assigned regimen because of adverse events was 8.9% in the darolutamide group and 8.7% in the placebo group. Darolutamide was not associated with a higher incidence of seizures, falls, fractures, cognitive disorder, or hypertension than placebo. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, metastasis-free survival was significantly longer with darolutamide than with placebo. The incidence of adverse events was similar for darolutamide and placebo. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [18]
The Secondary End Points section (p. 1243) reports lower mortality with darolutamide than placebo in an interim overall-survival analysis of this phase 3 trial. But the paper does not establish the claimed survival benefit across multiple trials: its introduction (p. 1236) says the other androgen-receptor inhibitor trials showed longer metastasis-free survival and that their overall-survival data were still immature. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
Fizazi, K. S., Tran, N., Fein, L. E., Matsubara, N., Rodríguez-Antolín, A., Alekseev, B. Y., Özgüroğlu, M., Ye, D., Feyerabend, S., Protheroe, A. S., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1704174 · Cited by 2,326 · see citing works
Self-citationScher, H. I., Halabi, S., Tannock, I. F., Morris, M. J., Sternberg, C. N., Carducci, M. A., Eisenberger, M. A., Higano, C. S., Bubley, G. J., Dreicer, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.4487 · Cited by 2,228 · see citing works
Abiraterone for prostate cancer not previously treated with hormone therapy
James, N. D., de Bono, J. S., Spears, M. R., Clarke, N. W., Mason, M. D., Dearnaley, D. P., Ritchie, A. W. S., Amos, C. L., Gilson, C., Jones, R. J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1702900 · Cited by 1,801 · see citing works
Bolla, M., González, D., Warde, P. R., Dubois, J. B., Mirimanoff, R., Storme, G. A., Bernier, J., Kuten, A., Sternberg, C. N., Gil, T., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707313370502 · Cited by 1,547 · see citing works
Apalutamide 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-citationAntitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study
Scher, H. I., Beer, T. M., Higano, C. S., Anand, A., Taplin, M., Efstathiou, E., Rathkopf, D. E., Shelkey, J., Yu, E. Y., Alumkal, J. J., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60172-9 · Cited by 1,063 · see citing works
Enzalutamide 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-citationGillessen, S., Attard, G., Beer, T. M., Beltran, H., Bossi, A., Bristow, R. G., Carver, B. S., Castellano, D., Chung, B. H., Clarke, N. W., et al. (2017) · European Urology · doi:10.1016/j.eururo.2017.06.002 · Cited by 645 · see citing works
Self-citationIntermittent Androgen Suppression for Rising PSA Level after Radiotherapy
Crook, J. M., O'Callaghan, C. J., Duncan, G. G., Dearnaley, D. P., Higano, C. S., Horwitz, E. M., Frymire, E., Malone, S. C., Chin, J. L., Nabid, A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1201546 · Cited by 498 · see citing works
Smith, 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
Self-citationvan Andel, G., Bottomley, A., Fosså, S. D., Efficace, F., Coens, C., Guerif, S. G., Kynaston, H., Gontero, P., Thalmann, G. N., Akdaş, A., et al. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.07.030 · Cited by 494 · see citing works
Halabi, S., Kelly, W. K., Ma, H., Zhou, H., Solomon, N. C., Fizazi, K., Tangen, C. M., Rosenthal, M., Petrylak, D. P., Hussain, M., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.65.7270 · Cited by 461 · see citing works
Self-citationGravis, G., Boher, J., Joly, F., Soulie, M., Albiges, L. K., Priou, F., Latorzeff, I., Delva, R., Krakowski, I., Laguerre, B., et al. (2015) · European Urology · doi:10.1016/j.eururo.2015.11.005 · Cited by 458 · see citing works
Self-citationMetastasis-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-citationMoilanen, A., Riikonen, R., Oksala, R., Ravanti, L., Aho, E., Wohlfahrt, G., Nykänen, P., Törmäkangas, O. P., Palvimo, J. J., & Kallio, P. J. (2015) · Scientific Reports · doi:10.1038/srep12007 · Cited by 384 · see citing works
Cella, D. F., Nichol, M. B., Eton, D. T., Nelson, J. B., & Mulani, P. M. (2008) · Value in Health · doi:10.1111/j.1524-4733.2008.00409.x · Cited by 213 · see citing works
Fizazi, K. S., Massard, C., Bono, P., Jones, R., Kataja, V. V., James, N. D., Garcia, J. A., Protheroe, A. S., Tammela, T. L. J., Elliott, T., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70240-2 · Cited by 198 · see citing works
Self-citationManaging 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-citationAlumkal, J. J., Sun, D., Lu, E., Beer, T. M., THOMAS, G. V., Latour, E. J., Aggarwal, R. R., Cetnar, J. P., Ryan, C. J., Tabatabaei, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922207117 · Cited by 145 · see citing works
Rajaram, P. S., Rivera, A., Muthima, K., Olveda, N., Muchalski, H., & Chen, Q. (2020) · Molecules · doi:10.3390/molecules25102448 · Cited by 65 · see citing works
Massard, C., Penttinen, H., Vjaters, E., et al. (2015) · European Urology · doi:10.1016/j.eururo.2015.09.046 · Cited by 62 · see citing works
Self-citationZurth, C., Sandman, S., Trummel, D., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.7_suppl.156 · Cited by 56 · see citing works
Zurth, C., Sandmann, S., Trummel, D., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.6_suppl.345 · Cited by 46 · see citing works
Shore, N. D., Tammela, T. L. J., Massard, C., Bono, P., Aspegrén, J., Mustonen, M. V. J., & Fizazi, K. S. (2017) · European Urology Focus · doi:10.1016/j.euf.2017.01.015 · Cited by 33 · see citing works
Self-citationTackling non-metastatic castration-resistant prostate cancer: special considerations in treatment
Anantharaman, A., & Small, E. J. (2017) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2017.1333903 · Cited by 33 · see citing works
Prostate Cancer in Latin America: Challenges and Recommendations
dos Reis, R. B., Alías-Melgar, A., Martínez-Cornelio, A., et al. (2020) · Cancer Control · doi:10.1177/1073274820915720 · Cited by 25 · see citing works
Fizazi, K. S., Massard, C., Bono, P., et al. (2017) · European Urology Focus · doi:10.1016/j.euf.2017.01.010 · Cited by 21 · see citing works
Self-citationNagaya, N., Kanayama, M., Nagata, M., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00495 · Cited by 9 · see citing works
Foucher, Y., Lorent, M., Tessier, P., Supiot, S., Sebille, V., & Dantan, É. (2018) · Health and Quality of Life Outcomes · doi:10.1186/s12955-018-0870-6 · Cited by 8 · see citing works
Impact and Outcomes of Pretreatment Total Serum Testosterone on Localized Prostate Cancer Patients
Usera, B. M., Creveling, P., & Tward, J. D. (2020) · Prostate Cancer · doi:10.1155/2020/8357452 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Parker, C., Castro, E., Fizazi, K., Heidenreich, A., Ost, P., Procopio, G., Tombal, B., & Gillessen, S. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.06.011 · Cited by 977 · see citing works
Self-citationEnzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer
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., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2003892 · Cited by 428 · 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
Self-citationFizazi, K., & Gillessen, S. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.02.015 · Cited by 119 · see citing works
Self-citationMaurice Dror, C., Chi, K. N., & Khalaf, D. J. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-1341 · Cited by 14 · see citing works
Li, 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
Imaging and therapy in prostate cancer using prostate specific membrane antigen radioligands
Naik, M., Khan, S. R., Lewington, V., Challapalli, A., Eccles, A., & Barwick, T. D. (2024) · British Journal of Radiology · doi:10.1093/bjr/tqae092 · Cited by 10 · see citing works
- Authors
- Fizazi, K., Shore, N., Tammela, T. L., Ulys, A., Vjaters, E., Polyakov, S., Jievaltas, M., Luz, M., Alekseev, B., Kuss, I., Kappeler, C., Snapir, A., Sarapohja, T., & Smith, M. R.
- Affiliations
- Université Paris-Sud (FR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-03-28
- Volume
- 380
- Issue
- 13
- Pages
- 1235-1246
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2913767564
- Cited by
- 930
- References
- 30
- Citations by year
- 2026: 68 · 2025: 97 · 2024: 112 · 2023: 109 · 2022: 138 · 2021: 176 · 2020: 152 · 2019: 71 · 2017: 1 · 2014: 1
- FWCI
- 98.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lithuanian University of Health Sciences (submittedVersion)
- Tampere University Institutional Repository (Tampere University) (submittedVersion)
- Funders
- Bayer
- Orion 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
- darolutamide, castration-resistant prostate cancer, non-metastatic prostate cancer, androgen receptor antagonists, metastasis-free survival, overall survival, prostate-specific antigen, androgen deprivation therapy, adverse events, pain progression, seizure incidence, fatigue, drug safety and efficacy, prostate cancer treatment, ARAMIS trial
- MeSH terms
- Progression-Free Survival, Aged, Aged, 80 and over, Double-Blind Method, Fatigue, Humans, Male, Middle Aged, Pyrazoles, Quality of Life, Proportional Hazards Models, Prostate-Specific Antigen, Kaplan-Meier Estimate, Intention to Treat Analysis, Androgen Receptor Antagonists, Prostatic Neoplasms, Castration-Resistant
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
