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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.
You, Benoit; Purdy, Christopher; Copeland, Larry J; Swisher, Elizabeth M; Bookman, Michael A; Fleming, Gini; Coleman, Robert; Randall, Leslie M; Tewari, Krishnansu S; Monk, Bradley J; Mannel, Robert S; Walker, Joan L; Cappuccini, Fabio; Cohn, David; Muzaffar, Mahvish; Mutch, David; Wahner-Hendrickson, Andrea; Martin, Lainie; Colomban, Olivier; Burger, Robert A.
Afiliação
  • You B; Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, EMR UCBL/HCL 3738, Lyon, France GINECO, Paris, France.
  • Purdy C; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, GINECO-GINEGEPS, Lyon, France.
  • Copeland LJ; Clinical Trial Development Division, Biostatistics and Bioinformatics Department, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
  • Swisher EM; The Ohio State University, James Cancer Hospital, Columbus, OH.
  • Bookman MA; Division of Gynecologic Oncology, Department of Ob/Gyn, University of Washington, Seattle, WA.
  • Fleming G; Director, Gynecologic Oncology Therapeutics, Kaiser Permanente Northern California, San Francisco, CA.
  • Coleman R; Hematology and Oncology, The University of Chicago Medicine, Chicago, IL.
  • Randall LM; Chief Scientific Officer, US Oncology Research, The Woodlands, TX.
  • Tewari KS; Division of Gynecologic Oncology, Virginia Commonwealth University, School of Medicine, Richmond, VA.
  • Monk BJ; UC Irvine Medical Center, Orange, CA.
  • Mannel RS; HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ.
  • Walker JL; The University of Oklahoma, Oklahoma City, OK.
  • Cappuccini F; The University of Oklahoma, Oklahoma City, OK.
  • Cohn D; UC Irvine Medical Center, Orange, CA.
  • Muzaffar M; The Ohio State University, James Cancer Hospital, Columbus, OH.
  • Mutch D; Internal Medicine, East Carolina University, Greenville, NC.
  • Wahner-Hendrickson A; Washington University School of Medicine, Siteman Cancer Center, St Louis, MO.
  • Martin L; Division of Medical Oncology, Mayo Clinic, Rochester, MN.
  • Colomban O; Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA.
  • Burger RA; Mersana Therapeutics, Cambridge, MA.
J Clin Oncol ; 40(34): 3965-3974, 2022 12 01.
Article em En | MEDLINE | ID: mdl-36252167
PURPOSE: In 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. METHODS: In 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. RESULTS: KELIM 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). CONCLUSION: This 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).
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Paclitaxel Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Paclitaxel Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article