ete initial adjuvant therapy and most of these crossed in years 3 to 4. All of these patients were in Option 1. A total of 184 patients started extended adjuvant therapy with Femara (172 patients) or with another aromatase inhibitor (12 patients). To explore the impact of this selective crossover, results from analyses censoring follow-up at the date of the selective crossover (in the tamoxifen arm) are presented for the Monotherapy Arms Analysis (MAA).
The PCA allowed the results of Femara for 5 years compared with tamoxifen for 5 years to be reported in 2005 after a median follow-up of only 26 months. The design of the PCA is not optimal to eva luate the effect of Femara after a longer time (because follow-up was truncated in two arms at around 25 months). The Monotherapy Arms Analysis (ignoring the two sequential treatment arms) provided follow-up equally as long in each treatment and did not over-emphasize early recurrences as the PCA did. The MAA thus provides the clinically appropriate updated efficacy results in answer to the first primary question, despite the confounding of the tamoxifen reference arm by the selective crossover to Femara. The updated results for the MAA are summarized in Table 6. Median follow-up for this analysis is 73 months.
The Sequential Treatments Analysis (STA) addresses the second primary question of the study. The primary analysis for the Sequential Treatments Analysis (STA) was from switch (or equivalent time-point in monotherapy arms) + 30 days (STA-S) with a two-sided test applied to each pair-wise comparison at the 2.5% level. Additional analyses were conducted from randomization (STA-R) but these comparisons (added in light of changing medical practice) were under-powered for efficacy.
Table 5: Adjuvant Study - Patient and Disease Characteristics (ITT Population) Primary Core Analysis (PCA) Monotherapy Arms Analysis (MAA)
Femara tamoxifen Femara tamoxifen
N=4003 N=4007 N=2463 N=2459
Characteristic n (%) n (%) n (%) n (%)
Age (median, years) 61 61 61 61
Age range (years) 38-89 39-90 38-88 39-90
Hormone receptor status (%)
ER+ and/or PgR+ 99.7 99.7 99.7 99.7
Both unknown 0.3 0.3 0.3 0.3
Nodal status (%)
Node negative 52 52 50 52
Node positive 41 41 43 41
Nodal status unknown 7 7 7 7
Prior adjuvant chemotherapy (%) 24 24 24 24
Table 6: Updated Adjuvant Study Results - Monotherapy Arms Analysis (Median Follow-up 73 Months) Femara
N=2463 tamoxifen
N=2459 Hazard ratio
Events
(%) 5-year rate Events
(%) 5-year rate (95% CI) P
Disease-free survival1 ITT 445 (18.1) 87.4 500 (20.3) 84.7 0.87 (0.76, 0.99) 0.03
Censor 445 87.4 483 84.2 0.84 (0.73, 0.95)
0 positive nodes ITT 165 92.2 189 90.3 0.88 (0.72, 1.09)
1-3 positive nodes ITT 151 85.6 163 83.0 0.85 (0.68, 1.06)
>=4 positive nodes ITT 123 71.2 142 62.6 0.81 (0.64, 1.03)
Adjuvant chemotherapy ITT 119 86.4 150 80.6 0.77 (0.60, 0.98)
No chemotherapy ITT 326 87.8 350 86.1 0.91 (0.78, 1.06)
Systemic DFS2 ITT 401 88.5 446 |
