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Robert L. Coleman, MD, FACOG, FACS, professor and Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the use of veliparib in ovarian cancer.
Robert L. Coleman, MD, FACOG, FACS, professor and Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the use of veliparib in ovarian cancer.
PARP inhibitors have been evaluated in ovarian cancer since they were discovered to have preclinical efficacy in BRCA1/2-deficient tumors, says Coleman. There are 2 primary mechanisms of PARP: one is the catalytic engagement of PARP itself, and the second is that it can trap PARP onto the DNA. Veliparib is unique in that it is considered to be a relatively weak PARP trapper, says Coleman. As such, it can be given in combination with full-dose cytotoxic chemotherapy.
In the phase III VELIA trial, investigators confirmed that veliparib can be given with full-dose chemotherapy without prohibitive toxicity. Investigators planned to give carboplatin at an area under the curve of 6 and the paclitaxel regimen at 80 mg/m2 weekly, or at 175 mg/m2 every 3 weeks.
When veliparib was given at a reduced dose, the carboplatin dose intensity was maintained at about 80% to 85% among all 3 arms, the weekly paclitaxel strategy was at about 80%, and the every-3-week strategy was at about 90%, falling within the parameters for full-dose intensity, concludes Coleman.