Chirag A. Shah, MD, details his personal clinical experience with using niraparib for ovarian cancer maintenance therapies.
Chirag A. Shah, MD: My personal clinical experience with niraparib has been extensive. I can tell you an anecdotal story of the first visit I had with a patient. I had seen the press release about the initial approval of niraparib in the platinum-sensitive recurrent setting. It was pretty amazing to think of an oral drug being given that could so greatly improve progression-free survival. I remember coming back to my office and having a patient bring the press release to discuss with me. She had a niece who was an oncology pharmacist, and she really wanted to dig into it. At that time, I had not had a great amount of experience with niraparib; that was probably a good 6 years ago. Since that point, I’ve both prescribed the medication to patients on a clinical trial, but also in my practice in several clinical settings. The drug is approved as we’ve discussed in the first-line setting for maintenance for patients who have had a response to platinum-based chemotherapy, but it’s also approved in later lines of therapy based off the NOVA trial. It’s approved for patients with platinum-sensitive recurrent ovarian cancer after platinum-based chemotherapy. But also after multiple lines of therapy, if they have a BRCA mutation or have deficiency in homologous recombination, they can benefit from it as a monotherapy based off the NOVA trial.
I’ve learned a great bit about managing the toxicities. When we first started treating patients with the drug, we didn’t have the more contemporary information on adjusting the dosing to a patient’s underlying weight and what their platelet counts are. I think one component that is critically important that we’ve learned, and this case was a good illustration of this, is allowing patients to recover from their hematologic toxicity associated with their first-line treatment. You’ve put a patient through intraperitoneal chemotherapy, or even if you’ve just given them standard intravenous therapy; their bone marrow, in a lot of cases, takes some time to recover. Thankfully due to our experience and my personal experience with prescribing this medication, our clinical pharmacy is well adept at putting patients on PARP inhibitor maintenance. I’ll send the prescription to our oncology pharmacy, and we are able to have the drugs and dispense to our patients directly, and they’ll have the approval and be ready to go. I’ll have to remind my nurse and the pharmacy staff that we need my go-ahead before we can give it, because I really do think it’s important to make sure they’ve recovered from that toxicity.
Separately, it’s important to stay on top of the laboratory tests, at least initially, getting those weekly CBCs [complete blood counts] so that you can get ahead of any potential thrombocytopenia or other hematologic toxicities you might encounter. Starting the patient on the appropriate dose: if their weight is under 170 lb, or if their platelet count at the time you want to initiate or when they finish chemotherapy is below 150, starting them at that 200-mg dose or 2 capsules daily is FDA approved. I remember working on the clinical trial PRIMA when this amendment occurred, and we were able to treat people on trial. Now we are taking that from that clinical trial experience to the actual day-to-day treatment of our patients. I will use the appropriate dose for the patient. If they’re above that weight and have normal platelets and haven’t experienced hematologic toxicity, I’m very comfortable starting those patients at the FDA recommended dose of 300 mg. I tend to have fairly manageable toxicities that are consistent with what we see, but a big part of it is counseling.
I begin the discussion about maintenance therapy at the initial presentation when I meet the patient, when we talk about what their disease course is going to look like. I feel like it’s important to not just throw this on them at the end when they’ve gone through a large operation and had chemotherapy, to circle back and say, “By the way, you’re also going to have 3 years of an additional medication.” I think you really need to set the expectations; there’s a lot going on at that initial diagnosis. You’re talking about surgery and chemotherapy. I may not spend a tremendous amount of time getting into the exact intricacies, but I’ll frequently mention that there is an oral drug that’s approved that they can take that’s going to help keep this cancer from coming back. When we look at it historically, and it still continues to be the case, we’ve made a lot of progress in this area. The biggest issue isn’t always whether I can get a good response to chemotherapy and take the cancer away, it’s keeping it away, and that’s really where I feel like maintenance therapy is so valuable.
If a patient is responding to her niraparib maintenance, determining how long I’m going to keep her on that is really going to be more a question of progression. If a patient remains disease-free and hasn’t exhibited significant toxicities that I can’t manage with dose interruptions or reductions, that’s why starting on the right dose is so important. We can feel more comfortable keeping her on that dose for the full 3 years. We can do this confidently based upon the data that have been presented and available in the publications from NOVA and PRIMA, that modified dose doesn’t appear to affect efficacy. Then the hard question really becomes they don’t always want to stop, but staying consistent with the labeling for me is important. I usually paint the case to the patient that it’s an evolving area of research whether retreatment with a PARP is an option, but certainly if they don’t progress on their first-line PARP inhibitor, I would feel more comfortable retreating with PARP. So when you get to that 3-year mark, it’s easier to have that discussion, knowing that I might be able to reuse this medication.
One of the reasons that I feel strongly about potentially offering this to my patients in the front line is for those platinum-resistant patients off of a clinical trial, you may never get an option to give them a PARP inhibitor, unless they have a BRCA mutation. For our HRP [homologous recombination proficient] patients or BRCA wild-type HRD [homologous recombination deficiency] negative, you may never get the opportunity to give them a PARP inhibitor. That’s where I feel like starting the discussion about this early and considering it in a broad variety of patients is crucial.
Transcript edited for clarity.