Session 3: CLINICAL IMPACT OF TARGETED THERAPIES
ANTIANGIOGENIC AGENTS IN OVARIAN CANCER: 2015 Bradley J. Monk, MD, FACS, FACOG Professor and Director Division of Gynecologic Oncology Department of Obstetrics and Gynecology Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, a Dignity Health Member University of Arizona Cancer Center-Phoenix Arizona USA
[email protected]
Disclosure • I have received grants and honoraria from Roche, Amgen, and Glaxo SmithKline as an advisor, speaker, chairman and investigator • The medical claims that I am going to present are depending on evidence based medicine and my clinical expertise
Objectives • Outline the development of anti-vascular agents in ovarian cancer (new trials and new agents) – – – –
• • • •
Anti-VEGF Anti-Angiopoetin Vascular disrupting agents Other
Consider recent and future FDA approvals Discuss biomarker development Discuss the research of novel combinations Summarize best practice guidelines
4th Ovarian Cancer Consensus Conference 25 – 27 June 2010 UBC Life Sciences Institute, Vancouver, British Columbia
B-2 What Are the Promising Targets for Future Therapeutic Approaches?
• The most promising targets in clinical trials are angiogenesis and homologous recombination deficiency.
Int J Gynecol Cancer 2011: 21; 756-762
GOG#218
ICON-7
GOG-0218: Schema Arm Carboplatin (C) AUC 6 Front-line: Epithelial OV, PP or FT cancer • Stage III optimal (macroscopic) • Stage III suboptimal • Stage IV
n=1800 (planned)
Paclitaxel (P) 175 mg/m2 R A N D O M I Z E
I
Placebo Carboplatin (C) AUC 6
1:1:1
Paclitaxel (P) 175 mg/m2 BEV 15 mg/kg
Placebo
Carboplatin (C) AUC 6
Stratification variables: • GOG performance status (PS) • Stage/debulking status
Burger RA et al N Engl J Med. 2011 Dec 29;365(26):2473-83.
II
Paclitaxel (P) 175 mg/m2
III
BEV 15 mg/kg
Cytotoxic (6 cycles)
Maintenance (16 cycles)
15 months
GOG-0218: significantly increased PFS with continued bevacizumab compared with standard chemotherapy 1.0 Median PFS (months)
0.8
I CP + Pl Pl (n=625)
II CP + B15 Pl (n=625)
III CP + B15 B15 (n=623)
10.6
11.6
14.7
0.89 (0.78–1.02)
0.70 (0.61–0.81)
0.0437a