ctive Response Rate (CR+PR) 48 (30%) 29 (20%)
Odds Ratio for Response (95% CI) 1.79 (1.10, 3.00)
Hazard ratio less than 1 or odds ratio greater than 1 favors Femara; hazard ratio greater than 1 or odds ratio less than 1 favors tamoxifen.
Figure 3 shows the Kaplan-Meier curves for survival.
Figure 3 Survival by Randomized Treatment Arm
Legend: Randomized Femara: n=458, events 57%, median overall survival 35 months (95% CI 32 to 38 months)
Randomized tamoxifen: n=458, events 57%, median overall survival 32 months (95% CI 28 to 37 months)
Overall logrank P=0.5136 (i.e., there was no significant difference between treatment arms in overall survival).
The median overall survival was 35 months for the Femara group and 32 months for the tamoxifen group, with a P-value 0.5136. Study design allowed patients to cross over upon progression to the other therapy. Approximately 50% of patients crossed over to the opposite treatment arm and almost all patients who crossed over had done so by 36 months. The median time to crossover was 17 months (Femara to tamoxifen) and 13 months (tamoxifen to Femara). In patients who did not cross over to the opposite treatment arm, median survival was 35 months with Femara (n=219, 95% Cl 29 to 43 months) vs 20 months with tamoxifen (n=229, 95% Cl 16 to 26 months).
14.5 Second-Line Treatment of Advanced Breast CancerFemara was initially studied at doses of 0.1 mg to 5.0 mg daily in six non-comparative Phase I/II trials in 181 postmenopausal estrogen/progesterone receptor positive or unknown advanced breast cancer patients previously treated with at least antiestrogen therapy. Patients had received other hormonal therapies and also may have received cytotoxic therapy. Eight (20%) of forty patients treated with Femara 2.5 mg daily in Phase I/II trials achieved an objective tumor response (complete or partial response).
Two large randomized, controlled, multinational (predominantly European) trials were conducted in patients with advanced breast cancer who had progressed despite antiestrogen therapy. Patients were randomized to Femara 0.5 mg daily, Femara 2.5 mg daily, or a comparator (megestrol acetate 160 mg daily in one study; and aminoglutethimide 250 mg b.i.d. with corticosteroid supplementation in the other study). In each study over 60% of the patients had received therapeutic antiestrogens, and about one-fifth of these patients had an objective response. The megestrol acetate controlled study was double-blind; the other study was open label. Selected baseline characteristics for each study are shown in Table 15.
Table 15: Selected Study Population Demographics Parameter megestrol acetate aminoglutethimide
study study
No. of Participants 552 557
Receptor Status
ER/PR Positive 57% 56%
ER/PR Unknown 43% 44%
Previous Therapy
Adjuvant Only 33% 38%
Therapeutic +/- Adj. 66% 62%
Sites of Disease
Soft Tissue 56% 50%
Bone 50% 55%
Viscera 40% 44%
Confirmed objective tumor response (complete response plus partial response) was the primary endpoint of the trials. Responses were measured according to the Union Inter |
