Avastin - Abstract 1274: Impact of bevacizumab plus 5FU/LV with or without irinotecan on quality of life in patients with metastatic colorectal cancer
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 367
A. Chawla1, E. Holmgren1, B. Nelson1, D. Cella2, K. Yost2, H. Hurwitz3, F. Kabbinavar4, W. Novotny1, R. Mrad5
1Genentech, Inc., Pharmaceutical Business Strategy-Economics, South San Francisco, CA, USA
2Evanston Northwestern Healthcare & Northwestern University, Evanston, IL, USA
3Duke University Medical Center, Durham, NC, USA
4David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
5F. Hoffmann-La Roche, Pharmaceutical Business Strategy-Economics, Basel, Switzerland
Background:
In a phase III trial, patients were treated first line with irinotecan, 5-FU, LV (IFL) plus placebo (n = 411) or bevacizumab (BV; Avastin), a monoclonal antibody to VEGF, plus IFL (n = 402).
The addition of BV to IFL significantly prolonged progression-free survival (PFS) by 71% and overall survival (OS) by 30% [Hurwitz et al. J Clin Oncol 2004;22:2335–42].
In a phase II study, 209 subjects were randomized to 5-FU/LV+placebo (105) or 5-FU/LV+BV (104); addition of BV to 5-FU/LV significantly prolonged PFS [Kabbinavar et al. J Clin Oncol 2005;23: epub ahead of print February 28]. Evaluating changes in quality of life (QOL) was a secondary objective in both studies.
Methods:
QOL endpoints were pre-specified; these included time to deterioration in QOL (TDQ), measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) colon cancer subscale (CCS);
Trial Outcome Index (TOI-C); and FACT-C score.
QOL deterioration was prospectively defined based on a clinically meaningful decrease in scores: 3 points (CCS), 7 points (TOI-C), and 9 points (FACT-C).
Median TDQ was evaluated for subjects with baseline and post-baseline assessments using the stratified log-rank test.
Those who progressed or died before QOL declined were assigned TDQ of time to progression or death.
Those who did not die or experience documented QOL deterioration or disease progression/death were censored at time of last QOL assessment.
Those who discontinued without a post-baseline assessment or disease progression were censored at date of randomization.
Results:
In the pivotal trial, baseline scores were available for 127/122 (CCS), 125/122 (TOI-C), and 124/121 (FACT-C) patients in the IFL and IFL+BV arms, respectively.
There were no statistically significant differences in TDQ (CCS, TOI-C, or FACT-C) between treatment arms (Table 1).
In the phase II study, baseline scores were available for 77/89 patients in the 5-FU/LV and 5-FU/LV + BV arms, respectively.
Median TDQ as measured by TOI-C (p = 0.0477) and FACT-C score (p = 0.0159) was significantly prolonged for patients treated with 5-FU plus BV.
Table 1
Median TDQ (months)
CCS TOI-C FACT-C
Pivotal trial
IFL+placebo 2.73 3.29 3.94
IFL+BV 2.89 2.76 3.98
Phase II trial
FL+placebo 3.02 2.30 2.63
FL+BV 3.12 3.22 3.61
Conclusions:
When added to IFL, BV significantly prolonged OS and PFS without compromising QOL.
Analyses of secondary measures of TDQ (TOI-C and FACT-C score) suggest a QOL gain with an increase in PFS for subjects receiving BV with 5-FU/LV.
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