Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.

TitlePredictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.
Publication TypeJournal Article
Year of Publication2020
AuthorsSecord, Angeles Alvarez, Kirsten Bell Burdett, Kouros Owzar, David Tritchler, Alexander B. Sibley, Yingmiao Liu, Mark D. Starr, Chris J Brady, Heather A. Lankes, Herbert I. Hurwitz, Robert S. Mannel, Krishnansu S. Tewari, David M. O'Malley, Heidi Gray, Jamie N. Bakkum-Gamez, Keiichi Fujiwara, Matthew Boente, Wei Deng, Robert A. Burger, Michael J. Birrer, and Andrew B. Nixon
JournalClin Cancer Res
Volume26
Issue6
Pagination1288-1296
Date Published2020 03 15
ISSN1557-3265
KeywordsAdult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Biomarkers, Tumor, Carboplatin, Carcinoma, Ovarian Epithelial, Double-Blind Method, Female, Humans, Interleukin-6, Middle Aged, Ovarian Neoplasms, Paclitaxel, Survival Rate
Abstract

PURPOSE: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses.EXPERIMENTAL DESIGN: Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell-derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates.RESULTS: Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS ( = 0.007) and OS ( = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS ( < 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo.CONCLUSIONS: The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.

DOI10.1158/1078-0432.CCR-19-0226
Alternate JournalClin Cancer Res
Original PublicationPredictive blood-based biomarkers in patients with epithelial ovarian cancer treated with carboplatin and paclitaxel with or without bevacizumab: Results from GOG-0218.
PubMed ID31919136
PubMed Central IDPMC7073274
Grant ListU10 CA180868 / CA / NCI NIH HHS / United States
U10 CA027469 / CA / NCI NIH HHS / United States
UG1 CA233193 / CA / NCI NIH HHS / United States
UG1 CA233191 / CA / NCI NIH HHS / United States
U10 CA180822 / CA / NCI NIH HHS / United States
R21 CA185730 / CA / NCI NIH HHS / United States
UG1 CA189867 / CA / NCI NIH HHS / United States
UG1 CA233331 / CA / NCI NIH HHS / United States
U24 CA196067 / CA / NCI NIH HHS / United States
P30 CA014236 / CA / NCI NIH HHS / United States