The Evolving Role of PARP Inhibitors in Ovarian Cancer - Episode 8
Matthew Powell, MD: Niraparib has a little bit of a unique side effect profile and it has an increased risk of thrombocytopenia. This thrombocytopenia can happen early and rather fast, and it can be quite profound at times. So, we monitor these patients more closely than we do with the other PARP inhibitors, where they get weekly lab tests, at least for the first month. Really, at any time there’s a dose adjustment, we do weekly laboratory-studied CBC. We need to act when we start to see grade-1 platelet toxicity. We need to do dose reductions or dose holds, and again, that is well spelled out in the package insert.
Oliver Dorigo, MD, PhD: There are several other trials ongoing at this point with niraparib. The PRIMA trial is going to investigate the safety and efficacy for patients after completion of frontline chemotherapy. Those patients have to have a response to the first-line surgery and chemotherapy. Those patients will then be treated in a randomized controlled fashion with either niraparib or placebo as a maintenance therapy. So, this is a trial that’s going to really move niraparib, a PARP inhibitor, into the frontline treatment setting. And we certainly hope that we will see at least an increase in progression-free survival. My prediction will be, based on the data that we know from other studies, that niraparib will likely make a difference, hopefully very similar to what we have seen in the NOVA trial for all patients regardless of HRD status or BRCA1 and BRCA2 mutations.
Niraparib is also being tested in combination with bevacizumab and in combination with pembrolizumab, which is an immune checkpoint inhibitor. Both of those approaches do make a lot of sense. The bevacizumab trial is called the AVANOVA trial. Bevacizumab is an antiangiogenic agent that can further decrease the expression of genes that are involved in homologous recombination, simply by the virtue of depriving the tumor of blood supply. In that context, the PARP inhibitors actually might have better efficacy. So, the synergy here is biologically sound. We still have to see whether it works in patients.
The combination with immunotherapy in the TOPACIO trial, immune checkpoint inhibition with pembrolizumab, likewise makes biological sense because the PARP inhibitors might increase the expression of neoantigens, which we believe are highly important in predicting response to immunotherapy. So, we’ll see how these trials work out. The QUADRA trial is still a single-agent niraparib trial, which will look at the efficacy of niraparib in those patients who have recurrent ovarian cancer.
Transcript Edited for Clarity