Four RCTs were included in the review (n=2,309, range 353 to 906). The methodological quality was deemed good in all studies. Three studies reported reliable methods of randomisation and allocation concealment. Three studies reported double-blinding. None of the studies indicated selective outcome reporting. Withdrawals and dropouts and ITT analyses were reported in all four studies (one did not include all randomised participants in the ITT analysis).
Letrozole was associated with significantly better time to progression (HR 0.70, 95% CI 0.60 to 0.82), objective response rate (RR 0.65, 95% CI 0.52 to 0.82) and quality-adjusted time without symptoms or toxicity (Q-Twist difference=1.5, p<0.001) than tamoxifen in one RCT. There was no significant difference in overall survival between letrozole and tamoxifen (one RCT).
Exemestane was associated with significantly better objective response rate (RR 0.68, 95% CI 0.53 to 0.89) and progression-free survival (HR 0.87, 95% CI 0.70 to 1.08) than tamoxifen, but there was no difference in overall survival (one RCT).
Anastrozole was associated with significantly superior time to progression than tamoxifen in one trial (HR 1.42, 95% CI 1.15 to not reported), but not in another. Overall survival was not significantly different between groups in either trial.
Tamoxifen was associated with significantly more serious adverse events compared with exemestane (OR 0.61, 95% CI 0.38 to 0.97). Exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR 2.33, 95% CI 1.07 to 5.11).
Anastrozole was associated with significantly more total adverse events (OR 1.04, 95% CI 1.00 to 1.09) and hot flushes in comparison with tamoxifen (OR 1.39, 95% CI 1.03 and 1.89; one RCT). Another trial showed no significant differences in adverse events between anastrozole and tamoxifen.
No significant differences in adverse events were found between letrozole and tamoxifen.
Letrozole and exemestane were associated with improved objective response rate compared with anastrozole; there was no significant difference between the three aromatase inhibitors in overall survival and progression-free survival.