Page 3 - Castration-resistant prostate cancer (CRPC): CUA/CUOG

Guideline: CRPC management

steroidal anti-inflammatory) without visceral metastases,
abiraterone acetate significantly improved radiographic PFS
Guideline statements regarding nmCRPC (16.5 vs. 8.3 months) (HR 0.53; 95% CI 0.45–0.62; p<0.001)
and had a statistically significant 4.4-month improvement in
1. ADT should be maintained in the nmCRPC OS (HR 0.81; p=0.0033). 10,11 Abiraterone also significantly
state. First-generation androgen receptor antag- delayed time to pain progression, time to chemotherapy initi-
onists (i.e., bicalutamide, flutamide, etc.) should ation, time to opiate initiation, and deterioration of the Eastern
be discontinued if patients are receiving these Cooperative Oncology Group (ECOG) performance status.
agents (Level 3, Strong recommendation). In the post-docetaxel setting: Abiraterone acetate 1000
2. Men with high-risk nmCRPC, defined as a mg per day plus prednisone 5 mg twice daily is recom -
PSADT <10 months, with an estimated life mended in patients progressing on or after docetaxel-based
expectancy of greater than five years should be chemotherapy (Level 1, Strong recommendation).
offered apalutamide or enzalutamide (Level 1, In the post-docetaxel setting, abiraterone-prednisone
Strong recommendation). compared to placebo-prednisone significantly prolonged
3. In men with high-risk nmCRPC who are felt median OS by 4.6 months (15.8 vs. 11.2 months; HR 0.74;
to be unsuitable or refuse approved therapies, p=0.0001) in patients with mCRPC who had progressed after
observation or use of first-generation androgen docetaxel treatment. Moreover, all secondary endpoints pro-
receptor antagonists may be attempted (Level vided support for the superiority of abiraterone over pla-
3, Weak recommendation). cebo: median time to PSA progression (8.5 vs. 6.6 months;
4. For men with nmCRPC who are not considered HR 0.63; p<0.0001), radiographic PFS (5.6 vs. 3.6 months;
high-risk, observation or secondary hormonal HR 0.66; p<0.0001), confirmed PSA response rate defined
treatments may be attempted (Level 3, Weak as ≥50% reduction in PSA from the pretreatment baseline
recommendation). PSA (29% vs. 5.5%; p<0.0001), and objective response
5. Patients who are untreated for nmCRPC should by Response Evaluation Criteria in Solid Tumors (RECIST)
be followed with regular imaging every 6–12 (14.8% vs. 3.3%; p<0.0001). 12
months depending on PSADT (Level 3, Weak
recommendation). Enzalutamide
Enzalutamide is a potent multi-targeted androgen signalling
pathway inhibitor.
In the chemo-naive setting: Enzalutamide 160 mg per
day is recommended as first-line therapy for asymptom-
detected on conventional imaging should be considered atic or minimally symptomatic mCRPC (Level 1, Strong
for systemic therapy with demonstrated survival benefits. recommendation).
Patients with mCRPC should optimally receive multidisci- In asymptomatic or minimally symptomatic patients
plinary care to maximize survival and quality of life. Because (defined as pain that is relieved by acetaminophen or a non-
any treatment for advanced disease remains non-curative, steroidal anti-inflammatory), enzalutamide decreased the risk
patients with advanced prostate cancer should be encour- of radiographic progression or death by 81% (HR 0.19; 95%
aged to participate in clinical trials. CI 0.15–0.23; p<0.001) and the risk of death by 29% (HR
0.71; 95% CI 0.60–0.84; p<0.001) as compared with pla-
I. AR signaling therapeutic options cebo. The benefit of enzalutamide was demonstrated for all
In men with CRPC, phase 3 clinical trials have evaluated secondary endpoints, including time to initiation of cytotoxic
the role of abiraterone acetate and enzalutamide in both the chemotherapy, time to first skeletal-related event (SRE), best
chemo-naive and post-chemotherapy settings. overall soft tissue response (59% vs. 5%; p<0.001), time to
PSA progression (HR 0.17; p<0.001), and ≥50% PSA decline
Abiraterone acetate rate (78% vs. 4%; p<0.001). Enzalutamide also significantly
Abiraterone acetate is a potent and irreversible inhibitor of delayed time to pain progression, time to opiate initiation, and
CYP-17, a critical enzyme in androgen biosynthesis. deterioration of the ECOG performance status. 13,14
In the chemo-naive setting: Abiraterone acetate 1000 In the post-docetaxel setting: Enzalutamide 160 mg per day
mg/day plus prednisone 5 mg twice daily is recommended is recommended in patients progressing on or after docetaxel-
for first-line therapy for asymptomatic or minimally symp- based chemotherapy (Level 1, Strong recommendation).
tomatic mCRPC (Level 1, Strong recommendation). In patients previously treated with docetaxel, the trial
In asymptomatic or minimally symptomatic patients compared enzalutamide and placebo. The study demon-
(defined as pain that is relieved by acetaminophen or a non- strated a significant advantage in OS of 4.8 months (18.4

CUAJ • October 2019 • Volume 13, Issue 10 309