In a phase 1 clinical trial, veliparib, a (ADP-ribose) polymerase (PARP) inhibitor, combined with oral cyclophosphamide showed promising clinical activity in patients with BRCA-mutant solid tumors.
Investigators conducted a randomized phase 2 trial to define the relative contribution of PARP inhibition that was previously observed.
In this study, investigators looked to evaluate the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC).
There were 75 patients in the study that were randomly assigned to receive either veliparib with cyclophosphamide (n= 37) or cyclophosphamide alone (n=38). The results showed one complete response in each arm, and three partial responses (PR) in the combination arm and six in the cyclophosphamide arm.
A genetic sequence and expression analysis was performed on 221 genes involved in DNA repair and revealed that there was no significant genetic alteration associated with treatment benefit.
Overall, the authors concluded that the addition of veliparib to cyclophosphamide did not improve either response rate or the median progression free survival. However, for the first time, investigators found that single-agent low-dose cyclophosphamide provided some clinical activity in the treatment of HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers.
This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival.