Report in English with a Dutch summary (KCE reports 63A)

KCE reports 63 Breast Cancer 83
Study ID Ref Search
date
De Placido S
2005
Levine MN
2005
[92] 466 premenopausal
N+ women
[84] 710 pre- or
perimenopausal
women with N+
breast cancer
Land SR 2004 [183] 160 women with
node-negative and
HR-negative breast
Population Intervention Outcomes Results Comments Study
type
cancer
Fargeot P 2004 [184] 338 BC operable N+
elderly patients (> 65
years)
Bonadonna G
2004
[185] Operable breast
cancer ≥3 nodes
(a) CMF (CMF)
(b) Doxorubicin followed
by CMF(A => CMF)
(c) CMF followed by
groserelin + tamoxifen
(CMF => GT)
(d) Doxorubicin followed
by CMF followed by
goserelin + tamoxifen (A
=> CMF => GT)
Either cyclophosphamide/
epirubicin/ fluorouracil
(CEF)
Or Cyclophosphamide/
methotrexate/
fluorouracil (CMF)
AC (doxorubicin and
cyclophos) vs CMF
(Cyclophos,
methotrexate and 5 FU)
Tamoxifen alone (TAM)
versus epirubicin +
tamoxifen (EPI-TAM)
First study: CMF
(cyclophos, mehtotrexate
and 5FU) versus DOX
(doxorubicin) followed by
CMF (DOX->CMF)
Second study: DOX
followed by CMF (DOX-
>CMF)° versus
alternating DOX and
CMF (DOX/CMF)
Disease free
survival
Overall survival
Relapse free
survival (RFS)
Overall survival
(OS)
At a median follow-up of 72 months,
A=>CMF as compared to CMF significantly
improved disease-free survival (DFS) with a
multivariate hazard ratio (HR =0.740 (95%
confidence interval (CI): 0.556–0.986;
P=0.040) and produced a nonsignificant
improvement of overall survival (OS)
(HR=0.764; 95% CI: 0.489–1.193).
The addition of GT after chemotherapy
significantly improved DFS (HR=0.74; 95% CI:
0.555–0.987; P=0.040), with a nonsignificant
improvement of OS
(HR=0.84; 95% CI: 0.54–1.32).
The 10-year RFS is 52% for patients who
received CEF compared with 45% for CMF
patients (hazard ratio [HR] for CMF v CEF =
1.31; stratified log-rank, P = .007).
The 10-year OS for patients who received
CEF and CMF are 62% and 58%, respectively
(HR for CMF v CEF =1.18; stratified log-rank,
P = .085).
RCT High
Level of
evidence
Allocation concealment? RCT Moderate
QOL Not significant differences RCT High
DFS (disease free
survival)
OS
Long terms
results of
previous studies
Relapse free
survival
Total survival
The 6-year DFS rates were 69.3% with TAM
and 72.6% with EPI-TAM (P =.14). The
multivariate analysis shows a relative risk of
relapse of 1.93 (95% CI, 1.70 to 2.17) with
TAM compared with EPI-TAM (P = .005).
The 6-year OS, related to disease
progression, was 79.1% and 79.8%,
respectively (P =.41).
After a median observation of 210 months,
no statistically significant difference was
documented in the first study (relapse-free
survival hazard rate [HR], 1.06; total survival
HR, 1.03). In contrast, the delivery of DOX
first, followed by CMF significantly reduced
the risk of disease relapse (HR, 0.68; 95% CI,
0.54 to 0.87; P = .0017) and death (HR, 0.74;
95% CI, 0.57 to 0.95; P = .018) compared
with the alternating regimen.
2 RCTs activated in the
early 1980s
RCT
High
RCTs High