Editing Metastatic Hormone-Sensitive Prostate Cancer (section)

=== <span style="color:#ff0000">Androgen-receptor Antagonists</span> ===

==== <span style="color:#ff0000">Enzalutamide</span> ====
* <span style="color:#ff00ff">'''ENZAMET (Davis et al. NEJM 2019)'''</span>
** Population: 1125 patients with metastatic, hormone-sensitive prostate cancer
** '''Randomized to enzalutamide vs. placebo'''
** Primary outcome: OS
** Secondary outcomes: progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events
** Results:
*** Median follow-up: 34 months
*** OS significantly improved in enzalutamide arm (HR 0.67, 95% CI 0.52-0.86; absolute risk difference at 3-years: 8% (80% enzalutamide vs. 72% placebo)
*** PSA-PFS and clinical PFS significantly improved in enzalutamide arm
*** Fatigue and seizures more common in enzalutamide group
** [https://pubmed.ncbi.nlm.nih.gov/31157964/ Davis, Ian D., et al.] "Enzalutamide with standard first-line therapy in metastatic prostate cancer." ''New England Journal of Medicine'' 381.2 (2019): 121-131.
* <span style="color:#ff00ff">'''ARCHES (Armstrong et al. JCO 2019)'''</span>
** Population: 1150 patients with metastatic, hormone-sensitive prostate cancer
** '''Randomized to enzalutamide vs. placebo'''
** Primary outcome: radiographic progression-free survival
** Results:
*** Significantly improved radiographic progression-free survival with enzalutamide (HR, 0.39; 95% CI 0.30-0.50)
**** Improved in high-volume and low-volume disease
** [https://pubmed.ncbi.nlm.nih.gov/31329516/ Armstrong, Andrew J., et al.] "ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer." ''Journal of Clinical Oncology'' 37.32 (2019): 2974-2986.

==== <span style="color:#ff0000">Apalutamide</span> ====
* <span style="color:#ff00ff">'''TITAN (Chi et al. NEJM 2019)'''</span>
** Population: 525 patients with metastatic, hormone-sensitive prostate cancer
** '''Randomized to apalutamide vs. placebo'''
** Primary outcome: radiographic progression-free and overall survival
** Results:
*** Significantly improved radiographic progression-free and overall survival with apalutamide
** [https://pubmed.ncbi.nlm.nih.gov/31150574/ Chi, Kim N., et al.] "Apalutamide for metastatic, castration-sensitive prostate cancer." ''New England Journal of Medicine'' 381.1 (2019): 13-24.

==== <span style="color:#ff0000">Darolutamide</span> ====

*<span style="color:#ff00ff">'''ARASENS (Smith et al. NEJM 2022)'''</span>
**Population: 1306 patients with metastatic, hormone-sensitive prostate cancer
**'''Randomized to ADT + docetaxel +/- darolutamide'''
**Primary outcome: overall survival
**Results
***Significantly improved overall survival with darolutamide
**[https://pubmed.ncbi.nlm.nih.gov/35179323/ Smith, Matthew R., et al.] "Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer." ''New England Journal of Medicine'' (2022).