Avastin - Abstract 643: Clinical benefit of bevacizumab in responding and non-responding patients with metastatic colorectal cancer
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 182
R. Mass1, S. Sarkar1, S.N. Holden1, H.I. Hurwitz2
1Genentech Inc, South San Francisco, CA; 2Duke University Medical Center, Durham, NC, USA
Background:
Bevacizumab (Avastin™), a monoclonal antibody to vascular endothelial growth factor (VEGF), is a potent anti-angiogenic agent with demonstrated survival benefit in first- and second-line metastatic colorectal cancer (mCRC), in combination with 5-FU/irinotecan or 5-FU/oxaliplatin.
Because preclinical data suggest bevacizumab is primarily a cytostatic agent, we explored the clinical benefit of bevacizumab assessed by progression-free survival (PFS) and overall survival (OS) in responding and non-responding subgroups.
Methods:
In the pivotal trial, 813 patients with untreated mCRC were randomized to receive irinotecan, 5-FU, and leucovorin (IFL) plus either bevacizumab or placebo.
For this retrospective, exploratory analysis, patients were divided into two groups; ``responders'' and ``non-responders'', which includes stable disease patients who remained on protocol therapy at day 180 without achieving a partial response/complete response or progressive disease, as well as patients who went off therapy within the first 180 days without a RECIST compliant tumor assessment.
For all analyses, PFS and OS within subgroups were estimated from Kaplan-Meier curves, and hazard ratios (HRs) for progression and death were estimated by Cox regression.
Results:
The bevacizumab and placebo arms in both the responding and non-responding subgroups had similar baseline characteristics.
Statistically significant improvements in HR for PFS and overall survival for bevacizumab-treated patients were observed in both subgroups (Table 1) and were consistent between the groups (interaction P-value for overall survival = 0.44; for PFS, 0.73).
Table 1
Best response Treatment n OR PFS
HR 95%CI HR 95%CI
All Subjects Bevacizumab + IFL 402 0.66 0.39–0.84 0.54 0.45–0.66
Placebo + IFL 411
Responders Bevacizumab + IFL 180 0.60 0.40–0.90 0.53 0.38–0.74
Placebo + IFL 143
Non-responders Bevacizumab + IFL 222 0.76 0.60–0.96 0.63 0.49–0.80
Placebo + IFL 268
Conclusions:
These analyses suggest that the magnitude of clinical benefit associated with bevacizumab treatment, as measured by HR for PFS and OS, is similar in mCRC, regardless of objective tumor response.
This response-independent survival benefit is a novel observation in mCRC, and has implications for endpoint selection in bevacizumab-based clinical trials and the routine clinical use of bevacizumab.
Data suggest that strategies of discontinuing bevacizumab in patients without an objective tumor response or at the time of maximal tumor response may compromise overall clinical benefit with respect to PFS and OS.
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