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Rationale for Chemotherapy Plus Veliparib in Frontline Treatment of Ovarian Cancers

Robert L. Coleman, MD
Published Online:6:30 PM, Tue October 8, 2019


Robert L. Coleman, MD, professor of medicine, The University of Texas MD Anderson Cancer Center, explains the rationale for the VELIA trial of veliparib (ABT-888) with frontline chemotherapy and maintenance in patients with high-grade ovarian cancer.
 
The phase III randomized, placebo-controlled, multinational trial was designed to evaluate the efficacy of veliparib in both the frontline and maintenance phases.
 
The trial was divided into 3 arms. The first arm received carboplatin and paclitaxel plus placebo followed by placebo maintenance. Arm 2 received carboplatin and paclitaxel plus veliparib followed by placebo maintenance. The third arm was the most significant for improving profession-free survival (PFS) meeting the endpoint of the trial. Patients in this arm received carboplatin and paclitaxel plus veliparib followed by veliparib maintenance.
 
With the combination of chemotherapy and veliparib, the investigators hoped to show that PARP could augment chemotherapy, Coleman says. The results showed that the addition of veliparib did improve PFS in these patients (23.5 vs 17.3 months in the control arm; HR, 0.68; 95% CI, 0.56-0.83; P <.001).
 
Coleman suggests that the success of this trial may be related to the unique characteristics of the drug, which includes 2 important mechanisms of action: the catalytic engagement of PARP and the ability to trap PARP onto the DNA. According to Coleman, as veliparib may be a weaker trapper of PARP, this allows the agent to be combined with chemotherapy for a greater cytotoxic effect. He points out that it is one of the few PARP inhibitors that is able to be combined with full-dose chemotherapy as a result.
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