Early switch with aromatase inhibitors as adjuvant hormonal therapy for postmenopausal breast cancer: pooled-analysis of 8794 patients.
BACKGROUND
The magnitude of the survival benefit of aromatase inhibitors (AIs) after 2-3 years of tamoxifen as adjuvant hormonal therapy for early breast cancer is still unclear. We performed a literature-based meta-analysis, to look how much advantages adjuvant the "early switch" strategy add over standard tamoxifen for 5 years.


METHODS
A pooled analysis of all phase-III trials was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. Significant differences in primary outcome (EFS and RFS, event- and relapse-free survival), and secondary outcomes (OS, overall survival, deaths without progression, other cancers and toxicities), were explored. Magnitude outcome measures were absolute benefits and number of patients needed to treat. Heterogeneity test was applied as well.


RESULTS
Five trials (8794 patients) were gathered. The risk of any event is reduced with AIs of 23%, with an absolute benefit of 3.8% (RR 0.67, 95% CI 0.59, 0.76). Again, RFS (RR 0.68, 95% CI 0.59, 0.79) or both LRFS and DFRS, were significantly improved with AIs. OS was significantly prolonged with AIs, with an absolute benefit of 1.2% (RR 0.76, 95% CI 0.62, 0.93), without significant heterogeneity. Bone fractures were significantly higher in patients receiving AIs (RR 1.50, 95% CI 1.12, 2.02), and endometrial cancer in patients who continued to receive tamoxifen (RR 0.32, 95% CI 0.13, 0.77), without significant heterogeneity.


CONCLUSIONS
The early switch strategy improves survival over standard tamoxifen for 5 years, with a different toxicity profile. The lack of significant heterogeneity in the analysis underscores the homogenous effect across all trials.
Bria
Emilio
E
Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Roma, Italy. emiliobria@yahoo.it
Ciccarese
Mariangela
M
Giannarelli
Diana
D
Cuppone
Federica
F
Nisticò
Cecilia
C
Nuzzo
Carmen
C
Natoli
Guido
G
Fabi
Alessandra
A
Terzoli
Edmondo
E
Cognetti
Francesco
F
Carlini
Paolo
P
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen