Fulvestrant 250 N=374
64 (N=239)
* 8 out of 374 patients (2.1%) shifted from fulvestrant 250 mg to fulvestrant 500 mg.
Summary of patients who had at least one SAE during the whole treatment period (main trial plus follow-up phase)
Previous data from phase II randomized studies testing Fulvestrant 500 mg: the NEWEST trial
Postmenopausal women with ER+ breast cancer (T2, 3, 4b, N0-3, M0); tumor >2 cm
Allowed prior hormonotherapy (HT)
Relapsing pts. “de novo” advanced pts.
X
X
1st line HT start adjuvant HT 5 yrs. 12 mos. gap
X X
1st line HT
Main patient and tumor characteristics
0.9
Faslodex 125 mg Faslodex 250 mg Anastrozole 1mg
100
1ng/ml
Proportion not progressed
Mean ± 1SEM
80
Conc. after: 2 weeks 1 week
0.8
0.7
2.5ng/ml
60
0.6
5ng/ml 7ng/ml 23ng/ml
Number (%) of patients Fulvestrant 500 mg N=361 Fulvestrant 250 mg N=374
Any SAE
35 (9.7)
8 (2.2)
27 (7.2)
4 (1.1)
Any causally related SAE
All events occurring after first dose are summarized Patients with multiple events in the same category were counted only once in that category Patients with events in more than one category were counted once in each of those categories
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival
Di Leo A et al. J Clin Oncol 2010; 28: 4594-4600
Secondary endpoint: overall survival (first analysis at 50% maturity – full analysis set)
0.6
0.4
0.2
0.0 0
4
8
12
16
20
24
28
32
36
40
44
48
Time (months) Patients at risk: 500 mg 250 mg 362 374 216 199 163 144 113 85 90 60 54 35 37 25 19 12 12 4 7 3 3 1 2 1 0 0
67 / 25 / 8
57 64 48
71 / 26 / 3
53 67 49
Primary endpoint: progression-free survival
1.0 Proportion of patients progression-free 0.8 Fulvestrant 500 mg Fulvestrant 250 mg HR = 0.80; 95% CI: 0.68, 0.94; p=0.006 Median PFS (months) Fulvestrant 500 mg 6.5 Fulvestrant 250 mg 5.5
Time To Progression (days)
J Robertson et al, Cancer Research 2001 DeFriend DJ, et al. Cancer Res. 1994;54:408 -414
500mg LA = 14ng/ml
Robertson JFR et al. Cancer 2003; 98: 229238
Optimal treatment of ER positive/HER-2 negative postmenopausal advanced breast cancer and future perspectives Angelo Di Leo
“Sandro Pitigliani” Medical Oncology Department Hospital of Prato Istituto Toscano Tumori, Prato, Italy
0.5
0.4
40
0.3
0.2
20
0.1
0
0
placebo
(n=29) (*n=19)
50mg
Faslodex (n=31)
125mg
Faslodex (n=32)
250mg
6mg
18mg
SA s/c (*n=12)
0
100
200
300
400
500
600
700
800
900
1000
Faslodex SA s/c (n=32) (*n=6)
Previous data suggesting an interaction between fulvestrant dose and activity
0018: Post-treatment Mean ER H-scores
120
1
20/21: Prospective Combined Analysis — Time to Progression
Di Leo A et al. J Clin Oncol 2010; 28: 4594-4600
Overall survival (final analysis at 75% maturity – full analysis set)
Proportion of patients alive 1.0 0.9 0.8 0.7
CONFIRM:
a phase III trial comparing Fulvestrant 250 mg vs 500 mg in post-menopausal women with ER + advanced disease
Trial design and main eligibility criteria
Fulvestrant 500 Fulvestrant 250 N=362 N=374 61 61 100 100
Age – median yrs. % ER+
% PgR+/ - / unknown
% visceral involvement % prior endocrine therapy - adjuvant setting - advanced setting
0.2
0.0 0 Patients at risk: 500 mg 250 mg 4
8
12
16
20
24
28
32
36
40
44
48
Time (months) 362 374 330 338 285 299 251 260 223 222 165 157 116 107 74 61 46 34 29 18 16 10 6 2 0 0
Proportion 1.0 of patients alive 0.8 Fulvestrant 500 mg Fulvestrant 250 mg
HR = 0.84; 95% CI: 0.69, 1.03; p=0.091
0.6
0.4 Median time to death (months) Fulvestrant 500 mg 25.1 Fulvestrant 250 mg 22.8
HR (95% CI) p-value
aNominal
Fulvestrant 500 mg Fulvestrant 250 mg
0.81 (0.69, 0.96) 0.016a
0.6
0.5 0.4 0.3 0.2 0.1 0
value, cannot be claimed as statistically significant
Baseline Tumor measurement by ultrasound; core biopsies taken
Open Label Randomisation 1:1
Fulvestrant HD
Fulvestrant AD
4 weeks Tumor measurement by ultrasound; core biopsies taken 16 weeks Ultrasound and surgery; pathological assessment of excised tumor 8-week post-surgery follow-up