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Sub-category:
Metastatic Breast Cancer
Category:
Breast Cancer--Metastatic Breast Cancer
Meeting:
2008 ASCO Annual Meeting
Session Type and Session Title:
null, General Session VI: Breast Cancer - Metastatic
Oral Presentation, Breast Cancer — Metastatic
Abstract No:
LBA1011^
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA1011^)
Author(s):
D. Miles, A. Chan, G. Romieu, L. Y. Dirix, J. Cortes, X. Pivot, P. Tomczak, T. Taran, N. Harbeck , G. G. Steger
Abstract:
Background: BV, an anti-angiogenic monoclonal antibody that prevents the biologic activity of VEGF, significantly improves overall (OS) and/or progression-free survival (PFS) in four tumour types. In patients with mBC, the phase III study E2100 demonstrated that BV in combination with paclitaxel as 1st-line therapy resulted in superior PFS compared with paclitaxel alone (hazard ratio [HR] = 0.48 as per independent review).The AVADO study investigated the combination of BV and D as first-line therapy in patients with locally recurrent or mBC. Methods: This randomised, double-blind phase III study compared D 100mg/m2 plus PL with D plus either BV 7.5mg/kg or BV 15mg/kg. D was administered q3w for up to 9 cycles. BV/PL was administered q3w until disease progression or unacceptable toxicity. The 1° endpoint was PFS, with 2° endpoints of OS, time to treatment failure, best overall response, duration of response, and safety. Key eligibility criteria were HER2-negative, inoperable locally recurrent or mBC; no prior chemotherapy for advanced disease; ECOG PS 0-1; adequate LVEF, and no CNS metastases. Statistical assumptions: 80% power for a 2-sided unstratified log-rank test to detect a HR for PFS of 0.7, for each BV arm compared with the PL arm (overall α=5%). Results: March 2006 to April 2007, 736 patients in 24 countries were randomised. With median follow-up of ~11 months PFS was statistically significantly superior for both BV containing arms compared with D alone. ORR was superior in both combination arms relative to D alone. OS is immature due to short follow up. Conclusions: Both doses of BV in combination with D significantly improved PFS and RR compared with D alone. BV added limited incremental toxicity relative to control. Safety results were comparable on the two BV arms and the overall findings did not reveal any new safety signals. | D + PL | D + BV 7.5mg/kg | D + BV 15mg/kg | | All randomised patients (n) | 241 | 248 | 247 | Unstratified HR vs D + PL (95% CI)
p-value (log-rank test)* | | 0.79 (0.63, 0.98)
0.0318 | 0.72 (0.57, 0.90)
0.0099 | | PFS | Stratified HR vs D + PL† (95% CI)
p-value (log-rank test)* | | 0.69 (0.54, 0.89)
0.0035 | 0.61 (0.48, 0.78)
0.0001 | Response rate (CR + PR) (%)‡
p-value vs D + PL | 44.4
- | 55.2
0.0295 | 63.1
0.0001 | | Safety population (n) | 233 | 250 | 247 | Grade >3 adverse events (%)
Grade >3 hypertension (%)
Grade >3 arterial thromboembolic events (%)
Grade >3 GI perforation (%)
Grade >3 CHF (%)
Grade >3 febrile neutropenia (%) | 67.0
1.3
0.4
0.9
-
12.0 | 74.8
0.4
-
0.4
0.8
15.2 | 74.1
3.2
-
0.4
-
16.6 | Any grade 5 adverse event (up to 21 days after
last dose) (%) | 2.6 | 1.6 | 1.6 | *p-values adjusted for multiple testing
†pre-specified stratified analysis with censoring for additional anti-neoplastic therapy that started prior to disease progression
‡in patients with measurable disease at baseline (n = 614; D + PL: 207; D + BV 7.5mg/kg: 201; D + BV 15.0mg/kg: 206) |
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by D. Miles:
Presentations by D. Miles:
Educational Book Manuscripts by D. Miles:
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