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Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials.

Ferretti G, Bria E, Giannarelli D, Felici A, Papaldo P, Fabi A, Di Cosimo S, Ruggeri EM, Milella M, Ciccarese M, Cecere FL, Gelibter A, Nuzzo C, Cognetti F, Terzoli E, Carlini P - Br. J. Cancer (2006)

Bottom Line: 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.Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. gia.fer@flashnet.it

ABSTRACT
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.

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Related in: MedlinePlus

Aromatase inhibitors vs tamoxifen: ORR. AI: aromatase inhibitors; TAM: tamoxifen; Ntot: total number of patients; RR: relative risk; Fixed: fixed effects model; Random: random effects model; ORR: overall response rate.
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fig1: Aromatase inhibitors vs tamoxifen: ORR. AI: aromatase inhibitors; TAM: tamoxifen; Ntot: total number of patients; RR: relative risk; Fixed: fixed effects model; Random: random effects model; ORR: overall response rate.

Mentions: We compared AI vs Tam in the overall population (2787 patients), using the FEM first. A significant advantage in ORR in favour of AI over Tam was detected (RR=1.13, 95% confidence interval (CI) 1.00–1.28, P=0.042) (Table 2 and Figure 1). The same impact in favour of AI was seen for TTP (2549 patients), where RR was 0.88 (95% CI 0.80–0.96, P=0.007) (Table 2 and Figure 2). Moreover, concerning CB, a statistically significant advantage in favour of AI compared with Tam was observed (RR 1.11, 95% CI 1.04–1.19, P=0.001). On the contrary, no significant difference was registered for OS (RR 0.97, 95% CI 0.79–1.18, P=0.743) (Table 2). A significant heterogeneity for ORR (0.03), TTP (<0.0001), and CB (<0.0001) was registered using the FEM (Table 2). At the REM, the significant improvement in ORR, TTP, and CB in favour of AI over Tam was not confirmed. By contrast, no significant heterogeneity was observed regarding OS estimates (Table 2).


Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials.

Ferretti G, Bria E, Giannarelli D, Felici A, Papaldo P, Fabi A, Di Cosimo S, Ruggeri EM, Milella M, Ciccarese M, Cecere FL, Gelibter A, Nuzzo C, Cognetti F, Terzoli E, Carlini P - Br. J. Cancer (2006)

Aromatase inhibitors vs tamoxifen: ORR. AI: aromatase inhibitors; TAM: tamoxifen; Ntot: total number of patients; RR: relative risk; Fixed: fixed effects model; Random: random effects model; ORR: overall response rate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361349&req=5

fig1: Aromatase inhibitors vs tamoxifen: ORR. AI: aromatase inhibitors; TAM: tamoxifen; Ntot: total number of patients; RR: relative risk; Fixed: fixed effects model; Random: random effects model; ORR: overall response rate.
Mentions: We compared AI vs Tam in the overall population (2787 patients), using the FEM first. A significant advantage in ORR in favour of AI over Tam was detected (RR=1.13, 95% confidence interval (CI) 1.00–1.28, P=0.042) (Table 2 and Figure 1). The same impact in favour of AI was seen for TTP (2549 patients), where RR was 0.88 (95% CI 0.80–0.96, P=0.007) (Table 2 and Figure 2). Moreover, concerning CB, a statistically significant advantage in favour of AI compared with Tam was observed (RR 1.11, 95% CI 1.04–1.19, P=0.001). On the contrary, no significant difference was registered for OS (RR 0.97, 95% CI 0.79–1.18, P=0.743) (Table 2). A significant heterogeneity for ORR (0.03), TTP (<0.0001), and CB (<0.0001) was registered using the FEM (Table 2). At the REM, the significant improvement in ORR, TTP, and CB in favour of AI over Tam was not confirmed. By contrast, no significant heterogeneity was observed regarding OS estimates (Table 2).

Bottom Line: 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.Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. gia.fer@flashnet.it

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus