The Role of PARP Inhibitors in the Management of Ovarian Cancer - Episode 3

Practice Pearl 1: Treatment Selection of PARP Inhibitors in Ovarian Cancer

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Bradley J. Monk, MD, FACS, FACOG, leads the discussion on approaching treatment selection of PARP inhibitors for the treatment of ovarian cancer.

Jennifer MacDonald, PharmD, BCOP: Dr Monk, as far as comparing the 3 PARP inhibitors, do you have experience with what you tend to frame when you’re talking about the 3 agents and how you discuss which one you might use for a given patient?

Bradley J. Monk, MD, FACS, FACOG: Yes. PARP inhibitors have been in the clinic since December 2014, so we’re 7 years into this, and I’ve thought a lot about this. There are some overlapping indications, where you have to choose. The overlapping indications are in the BRCA-mutated subset in the front line, where you can do PRIMA [trial regimen] niraparib or SOLO-1 olaparib. In the platinum-sensitive maintenance, you’ve got all 3 PARP inhibitors, which Sarah nicely said. And then in the treatment, you’ve also got all 3.

The most important factor in distinguishing them is the co-pay, because the money out of pocket can be substantial. If the co-pays were equal—they’re not—then the medications are very similar, both from an efficacy standpoint and almost from a toxicity standpoint. There’s this narrative out there that niraparib is more toxic from a bone marrow perspective. But with the individualized dose for patients who weigh less than 77 kg or 170 lb and have a platelet count of less than 150,000 per mm3—which almost never applies—these patients who start at 200 mg have a bone marrow suppression rate that’s very similar to the other PARP inhibitors.

Jennifer MacDonald, PharmD, BCOP: Yes, definitely. It’s good, and there have been even more studies coming out. Sarah, I don’t know if you can comment on this or if you’ve seen this, comparing financial toxicity and cost-effectiveness of these agents. Particularly in the last year, there has been a lot published on the cost-effectiveness.

Sarah Hayward, PharmD, BCOP: Yes, absolutely. Our approach is going to be, what indication are we treating, and what approvals do we have?

Bradley J. Monk, MD, FACS, FACOG: Exactly.

Sarah Hayward, PharmD, BCOP: That’s going to lead us down a particular path. Whereas in the recurrent maintenance setting or for treatment, we have all 3 open to us. And so you have considerations for the patients’ other comorbidities, how they have tolerated things, whether they’ve had a specific 1 line where their hemoglobin has really suffered vs whether their platelets really suffered in their prior therapies. Other medications and drug interactions come into play. But after that, if you do encounter high co-pays or things not being covered, it’s also a matter of being able to go down those paths of medication assistance programs, which are numerous. With the proper time and letters written and signatures gotten, we can usually get those for the patients, whatever the case.

Bradley J. Monk, MD, FACS, FACOG: To your point, olaparib is the only one metabolized by CYP3A. That’s important. And niraparib is the only once daily medication, which is very special. As both of you have nicely said, these aren’t the same medications. Just like oxaliplatin and carboplatin, or nab-paclitaxel, paclitaxel, or docetaxel, although we have these classes of agents, they’re not the same. Indication first, co-pay second, adverse reactions third. That’s been a big learning curve for us over the last 7 years.

Jennifer MacDonald, PharmD, BCOP: Yes, definitely. We touched on this earlier, but that molecular piece comes into it a lot, too, in helping guide you in which therapies you might be able to use for a given patient, depending on their mutations or lack thereof, which we’ll get into a little later. We’ve set the framework for these agents as a whole. We’re going to shift gears a bit into talking a little more about these in the frontline setting as opposed to in the recurrent or treatment setting, if you will. Are there any other concluding thoughts on the overview of these agents or anything else that either one of you would like to add to anything that we’ve discussed so far?

Bradley J. Monk, MD, FACS, FACOG: Other than the fact that they’re clearly oral, in the era of COVID-19, we’ve tried to keep patients out of the infusion center. And we’re going to talk about frontline therapy, because bevacizumab is in the mix, and it’s a good medication that should also be used earlier. PARP inhibitors should also be used earlier, but you’ve got to come to the infusion center in the middle of a pandemic to get bevacizumab. We can talk about that.

Jennifer MacDonald, PharmD, BCOP: Yes, definitely. And we can talk a little about the PAOLA-1 trial.

Transcript Edited for Clarity