Aflibercept

Clinical Cancer Research - Tập 19 Số 8 - Trang 1920-1925 - 2013
Kristen K. Ciombor1, Jordan Berlin1, Emily Chan1
1Authors' Affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee

Tóm tắt

Abstract Aflibercept, an intravenously administered anti-VEGF and antiplacental growth factor (PlGF) agent, has recently been approved by the U.S. Food and Drug Administration in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer who have previously received an oxaliplatin-containing chemotherapy regimen. In the phase III VELOUR trial, aflibercept plus FOLFIRI statistically significantly prolonged both progression-free survival (PFS; median PFS for the aflibercept plus FOLFIRI arm was 6.90 vs. 4.67 months for the placebo-plus-FOLFIRI arm) and overall survival (median overall survival for the aflibercept-plus-FOLFIRI arm was 13.50 vs. 12.06 months for the placebo plus FOLFIRI arm), but grade 3 or 4 adverse events were more common with the addition of aflibercept. However, the addition of aflibercept to 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in the phase II AFFIRM trial of first-line treatment of mCRC failed to improve PFS or response rate. As a decoy VEGF receptor, aflibercept (VEGF-Trap) has binding affinity for VEGF-A, VEGF-B, PlGF-1, and PlGF-2, and this is a mechanism of significant interest. Optimal strategies for incorporating aflibercept into treatment regimens that include other anti-VEGF and cytotoxic chemotherapeutic agents, as well as development of predictive biomarkers for treatment response, have yet to be defined. Clin Cancer Res; 19(8); 1920–5. ©2013 AACR.

Từ khóa


Tài liệu tham khảo

Holash, 2002, VEGF-Trap: a VEGF blocker with potent antitumor effects, Proc Natl Acad Sci U S A, 99, 11393, 10.1073/pnas.172398299

Hicklin, 2005, Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis, J Clin Oncol, 23, 1011, 10.1200/JCO.2005.06.081

Huang, 2003, Regression of established tumors and metastases by potent vascular endothelial growth factor blockade, Proc Natl Acad Sci U S A, 100, 7785, 10.1073/pnas.1432908100

Byrne, 2003, Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model, Clin Cancer Res, 9, 5721

Verheul, 2007, Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model, Clin Cancer Res, 13, 4201, 10.1158/1078-0432.CCR-06-2553

Lassoued, 2011, Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors, Cancer Biol Ther, 10, 1326, 10.4161/cbt.10.12.14009

Wachsberger, 2007, VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma, Int J Radiat Oncol Biol Phys, 67, 1526, 10.1016/j.ijrobp.2006.11.011

Chiron, 2007, Synergistic activity of aflibercept (VEGF Trap) in combination with 5-fluorouracil and irinotecan in preclinical tumor models, Proc from the AACR-NCI-EORTC: Mol Targets and Cancer Therapeutics

Gaya, 2012, A preclinical and clinical review of aflibercept for the management of cancer, Cancer Treat Rev, 38, 484, 10.1016/j.ctrv.2011.12.008

Lockhart, 2010, Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors, J Clin Oncol, 28, 207, 10.1200/JCO.2009.22.9237

Lu, 2008, Clinical pharmacokinetics of bevacizumab in patients with solid tumors, Cancer Chemother Pharmacol, 62, 779, 10.1007/s00280-007-0664-8

Mross, 2012, A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors, Clin Cancer Res, 18, 2658, 10.1158/1078-0432.CCR-11-1900

Van Cutsem, 2013, Phase I dose-escalation study of intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours, Eur J Cancer, 49, 17, 10.1016/j.ejca.2012.07.007

Khayat, 2013, Intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours: results from the expansion cohort of a phase I study, Eur J Cancer, 49, 790, 10.1016/j.ejca.2012.10.012

Tang, 2012, Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer, Clin Cancer Res, 18, 6023, 10.1158/1078-0432.CCR-11-3252

Van Cutsem, 2012, Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen, J Clin Oncol, 30, 3499, 10.1200/JCO.2012.42.8201

Hurwitz, 2004, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N Engl J Med, 350, 2335, 10.1056/NEJMoa032691

Macedo, 2012, Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups, BMC cancer, 12, 89, 10.1186/1471-2407-12-89

Bennouna, 2013, Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial, Lancet Oncol, 14, 29, 10.1016/S1470-2045(12)70477-1

Pericay, 2012, Phase 2 randomized, noncomparative open-label study of aflibercept and modified FOLFOX6 in the first line treatment of metastatic colorectal cancer (AFFIRM): Abstract O-0024, Ann Oncol, 23, iv5, 10.1016/S0923-7534(19)66488-4

Sobrero, 2012, Phase 3 CORRECT trial of regorafenib in metastatic colorectal cancer, Ann Oncol, 23, iv5, 10.1016/S0923-7534(19)66487-2

Ramlau, 2012, Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial, J Clin Oncol, 30, 3640, 10.1200/JCO.2012.42.6932

Riess, 2010, Double-blind, placebo-controlled randomized phase III trial of aflibercept plus gemcitabine versus placebo plus gemcitabine in patients with metastatic pancreatic cancer: final results, Proceedings from the 12th World Congress on Gastrointestinal Cancer

Pharmaceuticals S-AR, 2000, Aflibercept in combination with docetaxel in metastatic androgen independent prostate cancer (VENICE), Clinical Trialsgov Internet

Thông tin
Thông tin xuất bản

Clinical Cancer Research

Tập 19 Số 8

1920-1925

Thông tin tác giả