Page 4 - Castration-resistant prostate cancer (CRPC): CUA/CUOG

Saad et al

vs. 13.6 months; HR 0.62; p<0.0001) and in all secondary with patients, and therapy should be individualized based
endpoints, including confirmed PSA response rate (54% on patients’ clinical status and preferences (Level 3,
vs. 2%; p<0.001), soft-tissue response rate (29% vs. 4%; Weak recommendation).
p<0.001), time to PSA progression (8.3 vs. 3.0 months; HR Patients who do not respond to first-line ADT or who
0.25; p<0.001), radiographic PFS (8.3 vs. 2.9 months; HR progress clinically or radiologically without significant
0.40; p<0.001), and the time to the first SRE (16.7 vs. 13.3 PSA elevations may have neuroendocrine differentiation.
months; HR 0.69; p<0.001). 15 Biopsy of accessible lesions should be considered to identify
NOTE: The studies in the chemo-naive setting did not these patients; these patients should then be treated with
include patients with moderate or severe symptoms; how- combination chemotherapy, such as cisplatin/etoposide or
ever, abiraterone and enzalutamide may be potential thera- carboplatin/etoposide (Level 3, Weak recommendation).
peutic options in patients who are deemed chemotherapy-
ineligible or refuse chemotherapy (Expert opinion). Second-line systemic chemotherapy

II. Chemotherapy Cabazitaxel
Cabazitaxel is recommended for mCRPC patients pro -
First-line systemic chemotherapy gressing on or following docetaxel (Level 1, Strong
recommendation).
Docetaxel A phase 3 study comparing cabazitaxel to mitoxantrone
2
Docetaxel 75 mg/m intravenous (IV) every three weeks in patients previously treated with docetaxel has shown a
with 5 mg oral prednisone twice daily is recommended for statistically significant survival advantage. This random-
17
patients with mCRPC (Level 1, Strong recommendation). ized, placebo-controlled trial recruited 755 docetaxel-pre-
The TAX-327 study randomized 1006 patients to one of treated CRPC patients. OS was the primary endpoint of the
2
three treatment arms: 1) docetaxel 75 mg/m IV every three study. Patients were randomized to receive prednisone 10
weeks; 2) docetaxel 30 mg/m weekly for five of six weeks; mg/day with three times weekly mitoxantrone 12 mg/m or
2
2
2
or 3) control therapy with mitoxantrone. The study report- cabazitaxel 25 mg/m . An advantage in survival emerged
16
ed improved survival with docetaxel (every three weeks) in favor of the cabazitaxel group, with a median survival
compared with mitoxantrone-prednisone (median survival of 15.1 months compared with 12.7 months in the mito-
18.9 vs. 16.5 months; HR 0.76; 95% CI 0.62–0.94; two- xantrone group (HR 0.70; 95% CI 0.59, 0.83; p<0.0001). 17
sided p=0.009). No OS benefit was observed with docetaxel A recent phase 3 study comparing cabazitaxel 25 mg/
2
given on a weekly schedule (HR 0.91; 95% CI 0.75–1.11; m vs. 20 mg/m resulted in non-inferiority for cabazitaxel
2
two-sided p=0.36). Significantly, more patients treated with 20 mg/m with less adverse events. Of note, in the subgroup
2
docetaxel (every three weeks) achieved a pain response analysis of patients who had received both docetaxel and
compared with patients receiving mitoxantrone (35% vs. abiraterone/enzalutamide, results appeared to favor a higher
22%; p=0.01). Quality of life response, defined as a sus- dose of cabazitaxel. 18
tained 16-point or greater improvement from baseline on
two consecutive measurements, was higher with docetaxel Other options
given every three weeks (22% vs. 13%; p=0.009) or weekly For patients who have had a good response to first-line
(23% vs. 13%; p=0.005) compared with mitoxantrone. PSA docetaxel, re-treatment with docetaxel can be considered
response rates were also statistically significantly higher with (Expert opinion, Weak recommendation). 19,20
16
docetaxel compared to mitoxantrone. Although patients Mitoxantrone has not shown any survival advantage
received up to 10 cycles of treatment if no progression and but may provide symptomatic relief. Mitoxantrone may be
no prohibitive toxicities were noted, the duration of therapy considered a therapeutic option in symptomatic patients
should be based on the assessment of benefit and toxicities. with mCRPC in the first- or second-line setting (Expert
Rising PSA alone should not be used as the sole criteria opinion, Weak recommendation).
for progression; assessment of response should incorporate
clinical and radiographic criteria. III. Bone-targeted therapy
Alternative therapies that have not demonstrated
improvement in OS but can provide disease control, pal- Life-prolonging therapy
liation, and improve quality of life include weekly docetaxel
plus prednisone, and mitoxantrone plus prednisone (Level Radium-223
2, Weak recommendation). Radium-223 every four weeks for six cycles is recommended
The timing of docetaxel therapy in men with evidence in patients with pain due to bone metastases and who do not
of metastases but without symptoms should be discussed have visceral metastases (Level 1, Strong recommendation).

310 CUAJ • October 2019 • Volume 13, Issue 10