Selection of the treatment of PARP inhibitors in ovarian cancer

Jennifer MacDonald, PharmD, BCOP: Dr Monk, regarding the comparison of the 3 PARP inhibitors, do you have experience with what you tend to say when talking about the 3 agents and how you discuss which one you could 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 at 7 years old and I’ve thought about it a lot. There are overlapping indications, where you have to choose. The overlapping indications are in the BRCA-subset transferred to the first line, where you can do PRIMA [trial regimen] niraparib or SOLO-1 olaparib. In the platinum sensitive maintenance you have the 3 PARP inhibitors, which Sarah kindly said. And then in the processing, you also have the 3.

The most important factor in distinguishing them is the copayment, as the money in one’s pocket can be substantial. If the co-payers were equal — they are not — then the drugs are very similar, both in terms of efficacy and almost in terms of toxicity. There is this story that niraparib is more toxic from the point of view of the bone marrow. But with the individualized dose for patients weighing less than 77 kg or 170 lbs and having a platelet count less than 150,000 per mm3 which almost never applies, those patients who start at 200 mg have a suppression rate of bone marrow very similar to other PARP inhibitors.

Jennifer MacDonald, PharmD, BCOP: Definitely yes. That’s good, and there have been more studies coming out. Sarah, I’m not sure if you can comment on that, or if you’ve seen this, comparing the financial toxicity and cost effectiveness of these agents. Particularly over the past year, there have been a lot of profitability publications.

Sarah Hayward, PharmD, BCOP: Absolutely yes. Our approach is going to be, what indication are we dealing with and what approvals do we have?

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

Sarah Hayward, PharmD, BCOP: This will lead us on a particular path. While as part of recurring maintenance or for treatment we have all 3 open to us. And so you have considerations for other patients’ comorbidities, how they tolerated it, whether they had a specific line 1 where their hemoglobin really suffered versus whether their platelets really suffered from their previous therapies. Other drugs and drug interactions come into play. But after that, if you come across high copayments or things not covered, it’s also about being able to go through those avenues of drug assistance programs, of which there are many. Over time, the letters written and the signatures obtained, we can usually get them for the patients, whatever the case.

Bradley J. Monk, MD, FACS, FACOG: In your opinion, olaparib is the only one metabolized by CYP3A. It is important. And niraparib is the only drug once a day, which is very special. As you both kindly said, they are not the same drugs. Just like oxaliplatin and carboplatin, or nab-paclitaxel, paclitaxel, or docetaxel, although we have these classes of agents, they are not the same. Indication first, co-payment second, adverse effects third. It’s been a big learning curve for us over the past 7 years.

Jennifer MacDonald, PharmD, BCOP: Definitely yes. We talked about this earlier, but this molecular piece also comes into play to help you determine which therapies you might use for a given patient, based on their mutations or not, which we’re going to go into. a bit later. We have defined the framework for these agents as a whole. We’re going to shift gears a bit and talk a bit more as part of the first line rather than recurrence or processing, if you will. Are there any other final thoughts on previewing these agents or something else either of you would like to add to anything we’ve discussed so far?

Bradley J. Monk, MD, FACS, FACOG: Besides the fact that they are clearly oral, in the era of COVID-19 we have tried to keep patients out of the infusion center. And we’re going to talk about first line therapy, because bevacizumab is in the mix, and it’s a good drug that should also be used earlier. PARP inhibitors also need to be used earlier, but you need to go to the infusion center in the middle of a pandemic to get bevacizumab. We can talk about it.

Jennifer MacDonald, PharmD, BCOP: Definitely yes. And we can talk a bit about the PAOLA-1 trial.

Transcription edited for clarity

Martin E. Berry