Page 4 - Metastatic castration-naive and castration-sensitive prostate cancer: CUA/CUOG

So et al

in CHAARTED, patients were allowed to receive up to nine this translates to an absolute improvement in four-year
cycles compared to the six cycles in CHAARTED. There was survival of 9%.
no survival difference between the groups (58.9 months in the
combined group vs. 54.2 months in the ADT alone group; HR Abiraterone acetate (1000 mg daily) with prednisone
1.01; 95% CI 0.75–1.36). The differences in the outcomes of (5 mg daily) plus ADT is an option for mCNPC patients
the two studies is likely due to the differences in the burden with at least two of the three: Gleason score of ≥8, pres-
of disease in the two studies. Although 65% of patients in ence of three or more lesions on bone scan, or presence of
CHAARTED had high-volume metastases, less than 25% of measurable visceral metastasis (Level of evidence 1, Strong
the patients had low-volume disease. An unplanned post- recommendation).
hoc analysis of the high-volume cohort of GETUG-AFU 15
showed a non-significant trend toward improved OS in this Abiraterone acetate (1000 mg daily) with prednisone (5
23
cohort (39.8 vs. 35.1 months; HR 0.78; 95% CI 0.56–1.09). mg daily) plus ADT may be considered for patients with low-
A recent pooled analysis of both studies confirm the benefit volume mCNPC (Level of evidence 3, Weak recommendation).
of combined docetaxel and ADT in high-volume disease and
lack of benefit on low-volume metastatic burden. 24 Abiraterone acetate is a prodrug of abiraterone, which is a
The third trial to assess the impact of docetaxel in mCNPC/ CYP17A1 inhibitor; CYP17A1 is expressed in and is required
mCSPC was the docetaxel component of the STAMPEDE for androgen biosynthesis. Abiraterone acetate, when com-
trial. Unlike the CHAARTED and GETUG-AFU15 trials, bined with prednisone, was initially shown to improve
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patients with high-risk, non-metastatic PC were included. survival in mCRPC, both prior to and after docetaxel treat-
Eligible patients included: newly diagnosed metastatic, ment. 26,27 Two trials, LATITUDE and STAMPEDE, assessed
node-positive, or high-risk locally advanced (with high- the impact of abiraterone in mCNPC/mCSPC. 9,28,29 In the
risk features defined as at least two of: T3/4, Gleason score LATITUDE trial, 1199 patients were randomly assigned to
of 8–10, and PSA ≥40 ng/mL); or previously treated with either the abiraterone acetate (1000 mg) plus prednisone
radical surgery and/or radiotherapy with high-risk features. (5 mg) once daily orally or matching placebo plus ADT.
Of the 2962 patients randomized, 1817 (61%) men had Eligible patients included mCNPC with at least two of three
bony metastases and 592 patients received only ADT and high-risk features (Gleason score of ≥8, presence of three
six cycles of docetaxel (75 mg/m every three weeks for six or more lesions on bone scan, or presence of measurable
2
cycles). The combination of ADT and docetaxel had a sur- visceral metastasis except lymph node metastasis). Updated
vival advantage compared to ADT alone (HR 0.78; 95% CI OS data with median followup of 51.8 months showed that
0.66–0.93; p=0.006). Although patients were not classified OS was significantly longer in the abiraterone acetate plus
having high- or low-volume metastases, only patients with prednisone group (median 53.3 months [95% CI 48.2–not
metastatic disease had evidence of benefit with ADT and reached]) than in the placebo group (median 36.5 months
docetaxel (HR 0.76; 95% CI 0.62–0.92; p=0.005). [95% CI 33.5–40.0]), with a HR of 0.66 (95% CI 0.56−0.78;
A recent post-hoc, non-prespecified analysis of STAMPEDE p<0·0001). A post-hoc, exploratory analysis of the impact of
was published. Metastatic burden was assessable in only disease burden showed that OS was improved only in high-
25
76% of patients for the analysis (830 of 1086 patients) and volume disease (n=487 in the abiraterone acetate plus pred-
362 (44%) had low and 468 (56%) high metastatic burden. nisone and ADT, and 468 in the ADT only group; HR 0.62;
Although OS was neither statistically significant in low-bur- 95% CI 0.52−0.74; p<0·0001); however, only few patients
den nor in high-burden disease (HR 0.76; 95% CI 0.54–1.07; had low-volume disease in this study (n=110 in the abi-
p=0.107 vs. HR 0.81; 95% CI 0.64–1.02; p=0.064), the raterone acetate plus prednisone and ADT, and n=133 in the
authors found no evidence of heterogeneity of docetaxel ADT only group; HR 0.72; 95% CI 0.47−1.10; p=0.1242).
effect between metastatic burden subgroups (interaction In the abiraterone component of the STAMPEDE trial,
p=0.827). The authors concluded that upfront docetaxel the efficacy of abiraterone acetate and prednisolone was
is considered for mCNPC/mCSPC patients regardless of assessed in men with mCNPC. In this study, 1917 mCNPC
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metastatic burden. This retrospective analysis contradicts patients were enrolled with: newly diagnosed and meta-
the results of CHAARTED, but the authors point out that static, node-positive, or high-risk, locally advanced (with
this may be due to the larger number of de novo mCNPC/ at least two of following: cT3 or cT4, a Gleason score of
mCSPC (n=362) in the low-burden group compared to the 8–10, or PSA level ≥40 ng/mL), or disease that was previ-
low-burden group in the CHAARTED trial (n<160). ously treated with radical surgery or radiotherapy and was
A recent meta-analysis of CHAARTED, GETUG-AFU15, now relapsing with high-risk features (PSA >4 ng/mL with a
and STAMPEDE confirms the benefit of addition of docetax- doubling time of <6 months, a PSA level >20 ng/mL, nodal
el to ADT in mCNPC/mCSPC (HR 0.77; 95% CI 0.68–0.87; or metastatic relapse). Men were randomized to receive
p<0.0001). The authors of the meta-analysis show that abiraterone acetate (1000 mg daily) plus prednisolone

20 CUAJ • February 2020 • Volume 14, Issue 2