Switching to an AI after 5 years of tamoxifen

A large, double-blinded, randomized trial (CAN-NCIC-MA17 [NCT00003140]) of 5,187 patients compared the use of letrozole versus placebo in receptor-positive postmenopausal women who received tamoxifen for approximately 5 years (range, 4.5–6.0) years.[76][Level of evidence B1]

A large, double-blinded, randomized trial (CAN-NCIC-MA17 [NCT00003140]) of 5,187 patients compared the use of letrozole versus placebo in receptor-positive postmenopausal women who received tamoxifen for approximately 5 years (range, 4.5–6.0) years.[76][Level of evidence B1]

After the first planned interim analysis, when median follow-up for patients in the study was 2.4 years, the results were unblinded because of a highly significant (P < .008) difference in DFS (HR, 0.57), favoring the letrozole arm.[76]

A large, double-blinded, randomized trial (CAN-NCIC-MA17 [NCT00003140]) of 5,187 patients compared the use of letrozole versus placebo in receptor-positive postmenopausal women who received tamoxifen for approximately 5 years (range, 4.5–6.0) years.[76][Level of evidence B1]

After 3 years of follow-up, 4.8% of the women on the letrozole arm had developed recurrent disease or new primaries versus 9.8% on the placebo arm (95% CI for the difference, 2.7%–7.3%). Because of the early unblinding of the study, longer-term comparative data on the risks and benefits of letrozole in this setting will not be available.[77,78]

A large, double-blinded, randomized trial (CAN-NCIC-MA17 [NCT00003140]) of 5,187 patients compared the use of letrozole versus placebo in receptor-positive postmenopausal women who received tamoxifen for approximately 5 years (range, 4.5–6.0) years.[76][Level of evidence B1]

An updated analysis including all events before unblinding confirmed the results of the interim analysis.[79] In addition, a statistically significant improvement in distant DFS was found for patients who received letrozole (HR, 0.60; 95% CI, 0.43–0.84; P = .002). Although no statistically significant difference was found in the total study population, the lymph node-positive patients who received letrozole also experienced a statistically significant improvement in OS (HR, 0.61; 95% CI, 0.38–0.98; P = .04), although the P value was not corrected for multiple comparisons.

The NSABP B-33 trial (NCT00016432) that was designed to compare 5 years of exemestane with placebo after 5 years of tamoxifen was stopped prematurely when the results of CAN-NCIC-MA17 became available. At the time of analysis, 560 of the 783 patients who were randomly assigned to receive exemestane remained on that drug and 344 of the 779 patients who were randomly assigned to receive placebo had crossed over to exemestane.[80][Level of evidence B1]

The NSABP B-33 trial (NCT00016432) that was designed to compare 5 years of exemestane with placebo after 5 years of tamoxifen was stopped prematurely when the results of CAN-NCIC-MA17 became available. At the time of analysis, 560 of the 783 patients who were randomly assigned to receive exemestane remained on that drug and 344 of the 779 patients who were randomly assigned to receive placebo had crossed over to exemestane.[80][Level of evidence B1]

An intent-to-treat analysis of the primary study end point, DFS, demonstrated a nonsignificant benefit of exemestane (HR, 0.68; P = .07).