TY - JOUR
T1 - Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients
T2 - A pooled analysis of the randomised trials
AU - Ferretti, G.
AU - Bria, E.
AU - Giannarelli, D.
AU - Felici, A.
AU - Papaldo, P.
AU - Fabi, A.
AU - Di Cosimo, S.
AU - Ruggeri, E. M.
AU - Milella, M.
AU - Ciccarese, M.
AU - Cecere, F. L.
AU - Gelibter, A.
AU - Nuzzo, C.
AU - Cognetti, F.
AU - Terzoli, E.
AU - Carlini, P.
PY - 2006/6/19
Y1 - 2006/6/19
N2 - The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P=0.042), TTP (P=0.007), and CB (P=0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P=0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P=0.005) and vaginal bleeding (P=0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect.
AB - The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P=0.042), TTP (P=0.007), and CB (P=0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P=0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P=0.005) and vaginal bleeding (P=0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect.
KW - Aromatase inhibitors
KW - Endocrine therapy
KW - First-line
KW - Metastatic breast cancer
KW - Pooled analysis
KW - Postmenopausal
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U2 - 10.1038/sj.bjc.6603194
DO - 10.1038/sj.bjc.6603194
M3 - Article
C2 - 16736002
AN - SCOPUS:33745073082
VL - 94
SP - 1789
EP - 1796
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 12
ER -