NcXHF

EARLY CHEMOTHERAPY IN MEN WITH METASTATIC PROSTATE CANCER
TABLE 2. Randomized Clinical Trials of ADT with or without Docetaxel in Hormone-Naive Metastatic Prostate
Cancer
Trial, Accrual Period
No. of
Patients
Median Follow-up
(Months) Treatment Arms Median PFS (Months) Median OS (Months)
GETUG-AFU 15 36 , 2004–2008 385 82.9 A: ADT A: 12.9 A: 46.5
B: ADT docetaxel for 6 cycles B: 22.9 B: 60.9
(HR 0.72, p 0.0021) (HR 0.9, p 0.44)
E3805: CHAARTED 38 , 2006–2012 790 29 A: ADT A: 19.8 A: 44
B: ADT docetaxel for 6 cycles B: 32.7 B: 57.6
(HR 0.49; p 0.0001) (HR 0.61; p 0.0003)
Abbreviations: PFS, progression-free survival; OS, overall survival; ADT, androgen-deprivation therapy; HR, hazard ratio.
cetaxel; however, the primary endpoint of overall survival
was not signifıcantly different between the groups at 58.9
months for patients that received docetaxel plus ADT versus
54.2 months for those who were treated with ADT alone (HR
1.01; 95% CI, 0.75 to 1.36; p 0.955). On the contrary, the
addition of docetaxel to ADT did signifıcantly improve the
biochemical PFS (secondary endpoint), which was 22.9
months for the combined treatment group and 12.9 months
for those treated with ADT alone (HR 0.72; 95% CI, 0.57 to
0.91; p 0.005). Seventy-two serious adverse events were
reported in the group given ADT plus docetaxel: more frequently
neutropenia (21%), febrile neutropenia (3%), abnormal
liver function tests (2%), and neutropenia with
infection (1%). Four treatment-related deaths occurred in
the ADT plus docetaxel group. An updated report with
longer follow-up of the GETUG-AFU 15 trial was presented
at the 2015 Genitourinary Cancers Symposium. 36
With a median follow-up of 82.9 months, the median OS
was 60.9 months and 46.5 months in the ADT plus docetaxel
and ADT alone arms, respectively (HR 0.9; 95% CI,
0.7 to 1.2; p 0.44). In patients with high-volume disease,
median OS rates were 39 months in ADT plus docetaxel
arm and 35.1 months in the ADT alone arm (HR 0.8; 95%
CI, 0.6 to 1.2; p 0.35). 36
The GETUG-AFU 15 trial did not show statistically significant
survival benefıt to adding docetaxel to ADT for mH-
SPC. However, the overall survival trend and the HR in the
high-volume patients favors the docetaxel arm. The trial had
a relatively small sample size, 1 included a substantial percentage
of patients with good prognostic factors at baseline: 49%
of the patients in the ADT plus docetaxel group and 50% of
the patients treated with ADT alone. Another concern about
this trial is the unusually high toxicity reported, with more
than 10% incidence of grade 3 neutropenia and four deaths in
the group given ADT plus docetaxel; 21% of men who received
docetaxel plus ADT discontinued treatment because
of toxicity. Results may have also been affected by cross-over
treatments since 62% of patients given ADT alone received
docetaxel at progression, compared with 28% of patients
given ADT plus docetaxel who were re-treated with docetaxel.
Interestingly, the Kaplan-Meier curves for overall
survival seem to separate after 36 months of follow-up. However,
only 199 patients are at risk at 36 months, and 124 at 48
months.
Data Presented at the 2014 ASCO Annual Meeting
Plenary Session
The results of the E3805 (Chemo-Hormonal Therapy Versus
Androgen Ablation Randomized Trial for Extensive Disease
in Prostate Cancer [CHAARTED]) trial recently reported
by Sweeney et al 37 provide practice-changing evidence.
CHAARTED is a U.S. intergroup phase III trial in which 790
men with hormone-naive mHSPC received either ADT
alone or ADT with 75 mg/m 2 of docetaxel every 3 weeks for a
maximum of six cycles. At enrollment, patients were stratifıed
by extent of metastatic disease as high-volume or lowvolume;
high volume was defıned as visceral metastasis
and/or four or more bone metastases with at least one beyond
axial skeleton (pelvis and vertebral column). The primary
endpoint was OS, and secondary endpoints included time to
biochemical, radiographic, or symptomatic progressive disease
(PD) and time to radiographic or symptomatic PD. The
trial was fırst designed to include high-volume patients as
they have poor prognosis. Eligibility was subsequently expanded
to allow all patients with mHSPC.
The addition of docetaxel to ADT signifıcantly improved
overall survival; a median of 57.6 months in the ADT plus
docetaxel arm and 44.0 months in the ADT arm (HR 0.61;
95% CI, 0.47 to 0.80; p 0.0003). The survival improvement
was seen specifıcally in men with high-volume disease; median
OS was 49.2 months with docetaxel plus ADT compared
with 32.2 months with ADT, a difference of 17 months (HR
0.60; 95% CI, 0.45 to 0.81; p 0.0006). In men with lowvolume
disease, median OS had not been reached at the time
of the presentation. The secondary endpoints demonstrated
higher PSA responses ( 0.2 ng/mL) at 6 and 12 months in
the docetaxel plus ADT group (27.5% and 22.7%, respectively)
compared to the ADT alone group (14% and 11.7%,
respectively), longer median time to castration resistance
(20.7 months vs. 14.7 months) and longer median time to
clinical progression in favor or the combination arm; 32.7
months, compared to 19.8 months (p 0.0001).
With regard to toxicity, 6% of men receiving docetaxel plus
ADT experienced febrile neutropenia, 1% experienced sig-
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