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Identification of Patients with Ovarian Cancer Experiencing the Highest Benefit from Bevacizumab in the First-Line Setting on the Basis of Their Tumor-Intrinsic Chemosensitivity (KELIM): The GOG-0218 Validation Study
Author
You, B.Purdy, C.
Copeland, L.J.
Swisher, E.M.
Bookman, M.A.
Fleming, G.
Coleman, R.
Randall, L.M.
Tewari, K.S.
Monk, B.J.
Mannel, R.S.
Walker, J.L.
Cappuccini, F.
Cohn, D.
Muzaffar, M.
Mutch, D.
Wahner-Hendrickson, A.
Martin, L.
Colomban, O.
Burger, R.A.
Affiliation
HonorHealth Research Institute, University of ArizonaIssue Date
2022-10-17
Metadata
Show full item recordPublisher
Lippincott Williams and WilkinsCitation
You, B., Purdy, C., Copeland, L. J., Swisher, E. M., Bookman, M. A., Fleming, G., ... & Burger, R. A. (2022). Identification of patients with ovarian cancer experiencing the highest benefit from bevacizumab in the first-line setting on the basis of their tumor-intrinsic chemosensitivity (KELIM): the GOG-0218 validation study. Journal of clinical oncology, 40(34), 3965.Journal
Journal of Clinical OncologyRights
© 2022 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
PURPOSEIn patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7 v 20.6 months; hazard ratio [HR], 0.78). An external validation study in the GOG-0218 trial was performed.METHODSIn GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable < 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses.RESULTSKELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1 v 5.6 months; HR, 0.64; 95% CI, 0.53 to 0.78), and for OS (median: 35.1 v 29.1 months; HR, 0.79; 95% CI, 0.65 to 0.97).CONCLUSIONThis GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website). © American Society of Clinical Oncology.Note
Open access articleISSN
0732-183XPubMed ID
36252167Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1200/JCO.22.01207
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Except where otherwise noted, this item's license is described as © 2022 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License.
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