Background
Methods
Study design and setting
Patients
Inclusion criteria
Exclusion criteria
Treatments
Study drug
Dose regimen
Tumor response assessments and study visits
Statistical considerations and analysis
Sample size
Statistical analysis
Data presentation and analysis of baseline disease characteristics
Efficacy Analysis
Safety analysis
Analysis populations
Safety population
Intent-to-treat (ITT) population
Per-protocol (PP) population
Efficacy and safety assessments
Results
Patients
Disposition, baseline demographics, and disease characteristics
Mean ± SD | Median | (Range) | |
---|---|---|---|
Age (yrs) | 68.4 ± 7.2 | 67.0 | (56–85) |
Weight (kg) | 72.6 ± 16.4 | 68.5 | (49–120) |
BMI (kg/m2) | 27.2 ± 5.4 | 26.0 | (20.1–44.6) |
No. of patients | % of Safety population | |
---|---|---|
Clinical tumor categories | ||
T2* | 23 | 71.9 |
T3 | 5 | 15.6 |
T4a | 1 | 3.1 |
T4b | 3 | 9.4 |
Primary tumor histology
| ||
Ductal | 19 | 59.4 |
Invasive lobular/variant | 8/1 | 25.0/3.1 |
Other/missing | 3/1 | 9.4/3.1 |
Tumor grade
| ||
Well/moderately/poorly differentiated | 3/16/2 | 9.4/50.0/6.3 |
Missing | 11 | 34.4 |
Positive receptor status
| ||
Estrogen/progesterone/either | 31/25/32 | 96.9/78.1/100.0 |
Patient exposure
Months of treatment | ||||
---|---|---|---|---|
< 4 | 4 | > 4 | Total | |
No. of patients | 3 | 14 | 15 | 32 |
Median duration (range) (in days) | 65 (56–94) | 121 (105–130) | 214 (138–258) | 129.5 (56–258) |
Mean duration ± SD (in days) | 71.7 ± 19.9 | 120.1 ± 7.1 | 200.9 ± 46.4 | 153.5 ± 57.1 |
Treatment duration (months) | ||||
---|---|---|---|---|
Population | < 4 | 4 | > 4 | Total |
Safety | 3 (9.4%) | 14 (43.8%) | 15 (46.9%) | 32 |
Intent-to-treat (ITT) | n.a. | 14 (48.3%) | 15 (51.7%) | 29 |
Per-protocol (PP) | n.a. | 14 (56.0%) | 11 (44.0%) | 25 |
Analysis populations
Effect of treatment duration on tumor regression
Tumor response
Intent-to-treat population, N = 29 | Per-protocol population, N = 25 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Month 4 | Month 8 | Individual End | Month 4 | Month 8 | Individual End | |||||||
Tumor response
|
Clinical tumor assessment
|
Clinical tumor assessment
| ||||||||||
complete response | 1 |
(3.5%)
| 1 |
(3.5%)
| 2 |
(6.9%)
| 1 |
(4.0%)
| 1 |
(4.0%)
| 2 |
(8.0%)
|
partial response | 15 |
(51.7%)
| 6 |
(20.7%)
| 19 |
(65.5%)
| 14 |
(56.0%)
| 3 |
(12.0%)
| 16 |
(64.0%)
|
no change (stable disease) | 5 |
(17.2%)
| 1 |
(3.5%)
| 4 |
(13.8%)
| 3 |
(12.0%)
| 0 |
(0.0%)
| 3 |
(12.0%)
|
progressive disease | 2 |
(6.9%)
| 0 |
(0.0%)
| 3 |
(10.3%)
| 2 |
(8.0%)
| 0 |
(0.0%)
| 3 |
(12.0%)
|
Missing observations | 6 |
(20.7%)
| 21 |
(72.4%)
| 1 |
(3.5%)
| 5 |
(20.0%)
| 21 |
(84.0%)
| 1 |
(4.0%)
|
Tumor response
|
Mammography
|
Mammography
| ||||||||||
complete response | 0 |
(0.0%)
| 0 |
(0.0%)
| 0 |
(0.0%)
| 0 |
(0.0%)
| 0 |
(0.0%)
| 0 |
(0.0%)
|
partial response | 7 |
(24.1%)
| 2 |
(6.9%)
| 7 |
(24.1%)
| 5 |
(20.0%)
| 1 |
(4.0%)
| 5 |
(20.0%)
|
no change (stable disease) | 11 |
(37.9%)
| 1 |
(3.5%)
| 13 |
(44.8%)
| 10 |
(40.0%)
| 0 |
(0.0%)
| 11 |
(44.0%)
|
progressive disease | 1 |
(3.5%)
| 0 |
(0.0%)
| 1 |
(3.5%)
| 1 |
(4.0%)
| 0 |
(0.0%)
| 1 |
(4.0%)
|
Missing observations | 10 |
(34.5%)
| 26 |
(89.7%)
| 8 |
(27.6%)
| 9 |
(36.0%)
| 24 |
(96.0%)
| 8 |
(32.0%)
|
Tumor response
|
Breast ultrasound
|
Breast ultrasound
| ||||||||||
complete response | 1 |
(3.5%)
| 1 |
(3.5%)
| 2 |
(6.9%)
| 1 |
(4.0%)
| 1 |
(4.0%)
| 2 |
(8.0%)
|
partial response | 13 |
(44.8%)
| 5 |
(17.2%)
| 16 |
(55.2%)
| 11 |
(44.0%)
| 2 |
(8.0%)
| 13 |
(52.0%)
|
no change (stable disease) | 6 |
(20.7%)
| 1 |
(3.5%)
| 8 |
(27.6%)
| 5 |
(20.0%)
| 1 |
(4.0%)
| 7 |
(28.0%)
|
progressive disease | 1 |
(3.5%)
| 0 |
(0.0%)
| 1 |
(3.5%)
| 1 |
(4.0%)
| 0 |
(0.0%)
| 1 |
(4.0%)
|
Missing observations | 8 |
(27.6%)
| 22 |
(75.9%)
| 2 |
(6.9%)
| 7 |
(28.0%)
| 21 |
(84.0%)
| 2 |
(8.0%)
|
Comparison of tumor assessments
Treatment duration and tumor response
Reduction in tumor size
Relationship between treatment duration and tumor response
Clinical assessment | Mammography | Breast ultrasound | ||||
---|---|---|---|---|---|---|
ITT (n = 28) | PP (n = 24) | ITT (n = 21) | PP (n = 17) | ITT (n = 27) | PP (n = 23) | |
Pearson correlation
| r = -0.3146 | r = -0.4003 | r = -0.2396 | r = -0.2956 | r = -0.2099 | r = -0.3188 |
p = .1030 | p = .0526 | p = .2955 | p = .2494 | p = .2934 | p = .1382 | |
Spearman correlation
| r = -0.3839 | r = -0.5092 | r = -0.1037 | r = +0.0409 | r = -0.4111 | r = -0.3371 |
p = .0437 | p = .0110 | p = .6548 | p = .8761 | p = .0331 | p = .1158 | |
Multiple regression analysis
| F = 1.96 | F = 1.66 | F = 0.87 | F = 0.60 | F = 0.73 | F = 1.05 |
p = 0.1471 | p = 0.2070 | p = 0.4748 | p = 0.6278 | p = 0.5465 | p = 0.3928 | |
R2 = 0.1967 | R2 = 0.1996 | R2 = 0.1334 | R2 = 0.1212 | R2 = 0.0866 | R2 = 0.1424 | |
R2* = 0.0963 | R2* = 0.0795 | R2* = -0.0195 | R2* = -0.0816 | R2* = -0.0326 | R2* = 0.0070 |
Tumor staging, lymph nodes, and metastases
Clinical stage | Baseline | Individual End |
---|---|---|
T1a | -- | 1 (3.1%) |
T1b | -- | 1 (3.1%) |
T1c | -- | 7 (21.9%) |
T2 | 23 (71.9%) | 19 (59.4%) |
T3 | 5 (15.6%) | -- |
T4a | 1 (3.1%) | -- |
T4b | 3 (9.4%) | -- |
Missing | -- | 4 (12.5%) |
Subsequent breast surgery
Safety | ITT | PP | |||
---|---|---|---|---|---|
N = 32 | = 4 months (N = 14) | > 4 months (N = 15) | = 4 months (N = 14) | > 4 months (N = 11) | |
n (%)
| n (%)
| n (%)
| n (%)
| n (%)
| |
Lumpectomy | 22 (68.8%)
| 10 (71.4%)
| 12 (80.0%)
| 10 (71.4%)
| 8 (72.7%)
|
Mastectomy | 9 (28.1%)
| 4 (28.6%)
| 3 (20.0%)
| 4 (28.6%)
| 3 (27.3%)
|
Missing data | 1 (3.1%)
| -- | -- | -- | -- |
Total | 32 (100.0%)
| 14 (100.0%)
| 15 (100.0%)
| 14 (100.0%)
| 11 (100.0%)
|