capecitabine-naïve and in capecitabine pre-treated patient groups. The updated OS analysis showed a survival benefit for the eribulin group compared to TPC both in capecitabine pre-treated patients with a HR of 0.787 (95% CI: 0.645, 0.961), and for the capecitabine-naïve patients with a corresponding HR of 0.865 (95% CI: 0.606, 1.233).
The second Phase 3 study in earlier line metastatic breast cancer, Study 301, was an open-label, randomized, study in patients (n=1102) with locally advanced or metastatic breast cancer to investigate the efficacy of HALAVEN monotherapy compared to capecitabine monotherapy in terms of OS and PFS as co-primary endpoint. Patients had previously received up to three prior chemotherapy regimens, including both an anthracycline and a taxane and a maximum of two for advanced disease, with the percentage who had received 0, 1 or 2 prior chemotherapy treatments for metastatic breast cancer being 20.0%, 52.0% or 27.2% respectively. The HER2 status of the patients was: 15.3% positive, 68.5% negative and 16.2% unknown, whilst 25.8% of patients were triple negative.
Study 301 - Overall Survival (ITT Population)
Progression free survival assessed by independent review was similar between eribulin and capecitabine with medians of 4.1 months vs 4.2 months (HR 1.08; [95% CI: 0.932, 1.250]) respectively. Objective response rate as assessed by independent review was also similar between eribulin and capecitabine; 11.0% (95% CI: 8.5, 13.9) in the eribulin group and 11.5% (95% CI: 8.9, 14.5) in the capecitabine group.
The overall survival in patients in HER2 negative and HER2 positive patients in the eribulin and control groups in Study 305 and Study 301 is shown below:
Efficacy Parameter
Study 305 Updated Overall Survival ITT Population
HER2 Negative
HER2 Positive
HALAVEN
(n = 373)
TPC
(n = 192)
HALAVEN
(n = 83)
TPC
(n = 40)
Number of Events
285
151
66
37
Median months
13.4
10.5
11.8
8.9
Hazard Ratio (95% CI)
0.849 (0.695, 1.036)
0.594 (0.389, 0.907)
p-value (log rank)
0.106
0.015
Efficacy Parameter
Study 301 Overall Survival ITT Population
HER2 Negative
HER2 Positive
HALAVEN
(n = 375)
Capecitabine
(n = 380)
HALAVEN
(n = 86)
Capecitabine
(n = 83)
Number of Events
296
316
73
73
Median months
15.9
13.5
14.3
17.1
Hazard Ratio (95% CI)
0.838 (0.715, 0.983)
0.965 (0.688, 1.355)
p-value (log rank)
0.030
0.837
Note: Concomitant anti-HER2 therapy was not included in Study 305 and Study 301.
Efficacy Parameter
Study 305 Updated Overall Survival ITT Population
HER2 Negative
HER2 Positive
HALAVEN
(n = 373)
TPC
(n = 192)
HALAVEN
(n = 83)
TPC
(n = 40)
Number of Events
285
151
66
37
Median months
13.4
10.5
