ADT Plus Enzalutamide
Recommendation 1.7
➤ ADT plus enzalutamide should be offered to men with metastatic
noncastrate prostate cancer including both those with de novo
metastatic disease and those who have received prior therapies,
such as radical prostatectomy or radiotherapy for localized disease.
Enzalutamide plus ADT has demonstrated short-term survival benefits
(PSA progression-free, clinical progression-free, and overall) when
compared to ADT alone for men with metastatic noncastrate prostate
cancer as a group per ENZAMET (Strong recommendation; EB-B-H).
Recommendation 1.8
➤ The recommended regimen for men with metastatic noncastrate
prostate cancer is enzalutamide (160 mg per day) with ADT (Strong
recommendation; EB-B-H).
Qualifying Statements for ADT Plus Enzalutamide
• Among the subgroup of men with metastatic noncastrate prostate cancer previously
treated with docetaxel, it is currently unclear whether similar survival benefits
accrue long term when compared to treatment with first-generation antiandrogens
plus ADT since the final trial results for ENZAMET and ARCHES are not yet
available, though it is anticipated that the long-term results will confirm the early
findings. Early results (14.4 months median follow-up) from the ARCHES trial
show that the risk of radiographic disease progression or death was significantly
reduced with ADT plus enzalutamide versus ADT plus placebo overall as well as for
pre-specified subgroups, such as prior docetaxel versus no prior docetaxel and high-
volume disease versus low-volume disease. In the ENZAMET trial at 34 months,
none of the planned planned subgroup analyses for heterogeneity, as among those
receiving early docetaxel, were significant after adjusting for multiple comparisons.
Enzalutamide was FDA approved for use in the metastatic noncastrate prostate
cancer setting on December 16, 2019. Discussions with patients should include the
lack of data regarding long-term benefits and the cost of enzalutamide treatment
compared to other options such as abiraterone.
ADT Plus Apalutamide
Recommendation 1.9
➤ ADT plus apalutamide should also be offered to men with metastatic
noncastrate prostate cancer, including those with de novo metastatic
disease or those who have received prior therapy, such as radical
prostatectomy or radiotherapy for localized disease per TITAN (Strong
recommendation; EB-B-H).
