The Role of PARP Inhibitors in the Management of Ovarian Cancer - Episode 6

Practice Pearl 2: Overcoming Challenges for First-line Maintenance Therapy in Ovarian Cancer

, ,

Sarah Hayward, PharmD, BCOP, leads the discussion on common toxicities and when to create dose adjustments for first-line maintenance therapy in patients with ovarian cancer.

Jennifer MacDonald, PharmD, BCOP: Sarah, I want to go back to one of the points that you pointed out earlier about the quality of life for these patients and when they can expect most of the toxicities and things to improve. Based on your clinical experience and what we’ve seen in the clinical trials, can you comment in general on when these toxicities usually present themselves? Are they short-lived or long-lived? And when might we dose adjust for patients?

Sarah Hayward, PharmD, BCOP: Sure. Like I mentioned earlier, we’re going to see the majority of these toxicities early on, especially the nonhematological toxicities, but some of the hematological ones as well. Fatigue is a big thing that can hit patients right away along with nausea and other GI [gastrointestinal] adverse effects, including constipation and diarrhea. These are all things that we have some supportive care for to some degree. Even with fatigue, it’s about setting a reasonable expectation of fatigue. I always tell the patients, “Being tired where you can’t do as much as you want to and you maybe need to take an extra nap, but you can still carry on more or less with your life is different from being so fatigued you can’t get out of bed, function, nor take care of yourself.” These are differences. One I’m going to see if maybe we can push through, the other we need to address.

With the hematologic toxicities, any of these toxicities can come up at any time, but they’re more common with niraparib [Zejula]. The indications for that as far as laboratory monitoring that first month are pretty significant. We want to do a CBC [complete blood count] more frequently than just at baseline. We’d do this for all 3 of the medications in the class, but specifically for niraparib, we’re going to do the CBC at least once a week for that first month because we can see some pretty substantial drops in platelets and other things.

Hopefully we started with an appropriate dose based on the weights and plates, like they call it. It’s something to keep in mind. Depending on the patient, sometimes with olaparib [Lynparza] or rucaparib [Rubraca], even when we don’t have quite as close laboratory monitoring, we still do that with some patients if we’re a little worried about where they might go, depending on any history they’ve had or holds or dose reductions that were required. There’s definitely taking into consideration what the prescriber information is but also just some of the nuance on a case-by-case basis.

Jennifer MacDonald, PharmD, BCOP: Yes, definitely. Obviously, renal adjustments can come into play.

Sarah Hayward, PharmD, BCOP: Yes, correct. For olaparib, we need that for sure.

Jennifer MacDonald, PharmD, BCOP: And reductions as well. That could be another thing to consider. Dr Monk, I’m sure you’ve got all this memorized because I know how great your brain is, but one of the things that comes up sometimes is when to start. Each trial is a little different as far as when they required patients to start their PARP inhibitor. We’ve given people a bit of a break because they’re still recovering from chemotherapy and things of that nature. I don’t know if you can comment on the differences between when the PARP inhibitor was started from the completion of their chemotherapy that might help give you more of a window to bump those platelets a little or help improve fatigue or things from chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: Yes. Thank you for that. There are differences in the trials, but it’s pretty much been up to 8 weeks now. Particularly in patients on bevacizumab [Avastin], there’s a tendency because the bevacizumab in the PAOLA-1 regimen is continued. Just yesterday, I was in clinic and a patient was there for her sixth cycle. She has a BRCA1 mutation, and I believe in both medications for BRCA1 mutation, not just olaparib or niraparib. I said, “You’re going to be back here in 3 weeks for your bevacizumab and that will be too early for you to start your olaparib. Let’s plan on starting your olaparib in 6 weeks with your second dose of maintenance bevacizumab, and even then, we have some flexibility.”

There’s sometimes a misunderstanding that it takes time to recover. I’m not sure I’ve ever seen a patient with niraparib that didn’t recover her platelet count to 150,000 per mm3, because if she’s less than 150,000 per mm3, you probably should wait a little longer. Basically, the real indicator isn’t weight and platelets, it’s weight. And that’s 200 mg, Sarah, as you nicely said. It’s 8 weeks. Just to teach people, the other thing is that when you do a surgery, the target is 21 to 28 days for chemotherapy—closer to 21. If you’re starting chemotherapy more than 4 weeks after a debulking surgery, there’s a problem, because the cancer already grew back.

Jennifer MacDonald, PharmD, BCOP: Yes, it’s compromising care.

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

Jennifer MacDonald, PharmD, BCOP: Yes, definitely. We’ve utilized that as well. Sometimes the second cycle bevacizumab comes around, and that trial did give you 9 weeks technically to line up with that third cycle of bevacizumab, which is nice.

Bradley J. Monk, MD, FACS, FACOG: It is nice.

Jennifer MacDonald, PharmD, BCOP: It gives you some leeway to start.

Transcript Edited for Clarity