Biomarker analyses of second-line ramucirumab in patients with advanced gastric cancer from RAINBOW, a global, randomized, double-blind, phase 3 study
| Autor: | David Cunningham, S-E. Al-Batran, G. Bodoky, Alberto Sobrero, E. Van Cutsem, Rainbow Investigators, Jaffer A. Ajani, Rebecca R. Hozak, Stefano Cascinu, Sameera R. Wijayawardana, Zev A. Wainberg, David Ferry, Sang Cheul Oh, Symantha Melemed, A. Ohtsu, K. Muro |
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| Přispěvatelé: | Van Cutsem, E., Muro, K., Cunningham, D., Bodoky, G., Sobrero, A., Cascinu, S., Ajani, J., Oh, S. C., Al-Batran, S. E., Wainberg, Z. A., Wijayawardana, S. R., Melemed, S., Ferry, D., Hozak, R. R., Ohtsu, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Esophageal Neoplasms Paclitaxel Population Vascular Endothelial Growth Factor D Phases of clinical research Adenocarcinoma Placebo Antibodies Monoclonal Humanized Gastroesophageal junction cancer Predictive Prognostic Ramucirumab 03 medical and health sciences 0302 clinical medicine Double-Blind Method Stomach Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Medicine Humans education education.field_of_study business.industry Cancer Biomarker medicine.disease Prognosis Discontinuation 030104 developmental biology 030220 oncology & carcinogenesis Pharmacodynamics Biomarker (medicine) Esophagogastric Junction business Gastric cancer Follow-Up Studies |
| Popis: | BACKGROUND: The RAINBOW trial showed that second-line ramucirumab with paclitaxel prolongs overall survival (OS) and progression-free survival (PFS) compared with placebo plus paclitaxel for treatment of advanced gastric/gastroesophageal junction cancer. Plasma samples were collected from patients during the trial and tested to identify predictive and prognostic biomarkers. PATIENTS AND METHODS: Circulating factors in plasma samples from mutually exclusive subsets of RAINBOW patients were assayed using: Intertek assays (24 markers, 380 samples, 57% of patients) and Lilly-developed assay (LDA) platform (5 markers, 257 samples, 39% of patients). Time-trend plots were generated for each marker from the Intertek assays. Baseline patient data were dichotomized into low- and high-marker subgroups. Markers were analyzed for predictive effects using interaction models and for prognostic effects using main-effects models. RESULTS: The Intertek and LDA populations were representative of the full trial population. Plasma levels of VEGF-D and PlGF increased from baseline levels during treatment, then declined after treatment discontinued. Angiopoietin-2 exhibited a decrease during treatment, then increased after treatment discontinuation. No clear time trend was evident with the other markers. Analyses of baseline biomarker expression and its relationship with efficacy variables found no biomarker was predictive for efficacy outcomes, including VEGF-D. However, CRP, HGF, ICAM-3, IL-8, SAA, and VCAM-1 were identified as potential prognostic markers with low baseline levels corresponding to longer OS and PFS. CONCLUSIONS: Pharmacodynamic and prognostic relationships were found from the exploratory biomarker analyses in RAINBOW; however, no predictive markers for ramucirumab in gastric cancer were identified in this trial. ispartof: EUROPEAN JOURNAL OF CANCER vol:127 pages:150-157 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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