Editing Metastatic Hormone-Sensitive Prostate Cancer (section)

== Hormonal therapy ==
=== <span style="color:#ff0000">Inhibition of Androgen Synthesis</span> ===

==== <span style="color:#ff0000">Abiraterone</span> ====
* '''<span style="color:#ff00ff">STAMPEDE (James et al. NEJM 2017)</span>'''
** Population: 1917 patients had prostate cancer that was newly diagnosed and metastatic, node-positive, or high-risk locally advanced prostate cancer (with at least two of following: a tumor stage of T3 or T4, a Gleason score of 8 to 10, and a PSA level ≥40 ng per milliliter) or disease that was previously treated with radical surgery or radiotherapy and was now relapsing with high-risk features (in men no longer receiving therapy, a PSA level >4 ng per milliliter with a doubling time of <6 months, a PSA level >20 ng per milliliter, nodal or metastatic relapse, or <12 months of total ADT with an interval of >12 months without treatment)
** '''Randomized to ADT +/- abiraterone + prednisone'''
** Results:
*** Overall and failure-free survival significantly improved in abiraterone + ADT
** [https://pubmed.ncbi.nlm.nih.gov/28578639/ James, Nicholas D., et al.] "Abiraterone for prostate cancer not previously treated with hormone therapy." New England Journal of Medicine 377.4 (2017): 338-351.

* <span style="color:#ff00ff">'''LATITUDE (Fizazi et al. 2017)'''</span> 
** Population: 1199 patients with high-risk, metastatic, hormone-sensitive prostate cancer
*** '''<span style="color:#ff0000">High-risk required 2/3 high-risk factors:</span>'''
***# '''<span style="color:#ff0000">Visceral metastasis</span>'''
***# '''<span style="color:#ff0000">≥ 3 bone lesions</span>'''
***#* '''<span style="color:#ff0000">Recall, CHAARTED was ≥4 bone lesions with ≥ 1 beyond the vertebral bodies and pelvis</span>'''
***# '''<span style="color:#ff0000">Gleason score ≥ 8</span>'''
** '''Randomized to ADT +/- abiraterone + prednisone</span>'''
** Primary end points: OS and radiographic progression-free survival
** Results:
*** Median follow-up: 30 months
*** OS significantly improved in the abiraterone group (median not reached abiraterone vs. 34.7 months placebo) (HR 0.62)
*** Median length of radiographic progression-free survival significantly longer in the abiraterone group (33.0 months vs. 14.8 months placebo, HR 0.47)
** [https://pubmed.ncbi.nlm.nih.gov/28578607/ Fizazi, Karim, et al.] "Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer." New England Journal of Medicine 377.4 (2017): 352-360.

=== <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).