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Smith MR, Antonarakis ES, Ryan CJ, Berry WR, Shore ND, Liu G, et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort. Eur Urol. 2016;70:963–70.
•• Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378:1408–18 This reference is for the SPARTAN trial, which was a phase 3 clinical trial that led to the approval of apalutamide for nmCRPC. The primary endpoint was MFS, and apalutamide significantly improved MFS compared to placebo (40.5 m vs. 16.2 m, HR 0.28, 95% CI 0.23-0.35, P < 0.001).
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Smith MRMM, Nair S, Lawson J, Small, EJ. Association of metastasis-free survival (MFS) and overall survival (OS) in nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol 2018;36:Abstr 5032. This reference is for an abstract presented at the ASCO annual meeting in 2018. While it is only an abstract, the concept is critical for the approval of apalutamide and enzalutamide for nmCRPC. The data in this study suggests that MFS is associated with overall survival for patients with nmCRPC. This is the first study to show this association.
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Phase III trial of darolutamide in patients with non-metastatic castration-resistant prostate cancer meets primary endpoint. 2018. (Accessed November 20, 2018, 2018, at https://www.prnewswire.com/news-releases/phase-iii-trial-of-darolutamide-in-patients-with-non-metastatic-castration-resistant-prostate-cancer-meets-primary-endpoint-300736805.html.). This reference is for a press release that states that darolutamide met its primary endpoint of MFS in the phase 3 clinical trial ARAMIS. Darolutamide is a novel AR antagonist, and this result is expected to garner regulatory approval for darolutamide in the nmCRPC setting.