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FAQs: PARPis in OC
Pharmacists’ FAQs on the Use of PARP Inhibitors for Ovarian Cancer

Released: December 07, 2021

Expiration: December 06, 2022

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In this brief commentary, Colleen Bohnenkamp, PharmD, BCOP, BCPS, and Dane Fritzsche, PharmD, BCOP, answer questions on the management of ovarian cancer with PARP inhibitors that were submitted by an audience of healthcare professionals during a recent live ProCE webinar.

Are there any data to support retrial of a PARP inhibitor in the recurrent setting if used as frontline therapy?
Colleen Bohnenkamp, PharmD, BCOP, BCPS:
We have been pondering this question for a while. The results of the phase III OReO trial were presented at the 2021 European Society for Medical Oncology Congress. OReO evaluated maintenance olaparib rechallenge vs placebo in women who had received platinum-based therapy in the recurrent setting and had previously relapsed while receiving a PARP inhibitor. The study included patients with or without BRCA mutations, and we saw that olaparib rechallenge significantly improved progression-free survival in both groups. The current guidelines recommend no PARP inhibitor after previous progression on a PARP inhibitor, but this is an important question that needs to be explored further.

In your practice, do you ever switch between PARP inhibitors for tolerability?
Dane Fritzsche, PharmD, BCOP:
That is a good question, and it depends on what PARP inhibitor is being used and the particular adverse event. For example, if someone is receiving niraparib and their blood counts are not recovering even after dose reductions per the prescribing information, that might be a reason to switch. We frequently assess for cytopenia or neutropenia with niraparib, and if blood counts are a concern, it may be worth switching to a different PARP inhibitor, such as olaparib or rucaparib, both of which have fewer hematologic toxicity concerns. In addition, I have seen our provider switch between olaparib and rucaparib in cases of severe fatigue or nausea just to see if a different agent might be tolerable, but I am not aware of any data that support that.

How is homologous recombination deficiency (HRD) determined?
Colleen Bohnenkamp, PharmD, BCOP, BCPS:
There are a few different ways. The first is if a patient has a pathogenic germline or somatic mutation in one of the genes related to homologous recombination repair. Most commonly, gene mutations occur in BRCA1 or BRCA2, but several other genes—such as the CHEK1/2, PALB2, and RAD genes—are associated with homologous recombination repair, and mutations in these genes would result in HRD.

Another way to determine HRD is if the tumor is considered to have genomic instability. Determining genomic instability in a tumor sample is more complex but can be determined by calculating an HRD score, which takes into consideration loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions. 

What time of day do you instruct patients to take niraparib?
Dane Fritzsche, PharmD, BCOP:
Nausea can be a concern for patients receiving niraparib. To help them manage this adverse event, I usually recommend that they take their medication in the evening before they go to bed. This helps them sleep through that nausea or reduce its impact on activities of daily life. However, insomnia can be a unique adverse event with niraparib. If patients begin to experience insomnia, and nausea is not a concern, I may then recommend taking their medication in the morning to see if that helps with the nausea. If the patient is interested in trying this, we provide instructions on moving their administration times back over a few days. 

Is the response to PARP inhibitors as good for clear cell as for the other types of ovarian cancer?
Colleen Bohnenkamp, PharmD, BCOP, BCPS:
Most of the landmark trials only included patients with serous or endometrioid subtypes. Because clear cell subtypes were not included in the trials, we don’t know for certain. However, the National Comprehensive Cancer Network guidelines recommend consideration of maintenance PARP inhibitors in patients with BRCA1 or BRCA2 mutations.

How have you discussed the risk of acute myeloid leukemia with your patients?
Dane Fritzsche, PharmD, BCOP:
I have had patients express a concern regarding the risk of acute myeloid leukemia. They ask: “What is this risk? Have you seen it before?” And I refer to the data showing that it is seen in fewer than 1% of patients. I see how they respond to that answer, and if they still seem worried, I refer them back to their provider to have an in-depth discussion on that topic. I also tell them that this is not an adverse event I have personally seen yet, but it is a possibility in fewer than 1% of patients across the numerous studies performed.

Patients would receive a platinum-based regimen first and then, upon recurrence, would use the PARP inhibitors. Is that correct?
Colleen Bohnenkamp, PharmD, BCOP, BCPS:
Based upon the PARP inhibitors’ indications, patients would receive a platinum-based chemotherapy, and if they had complete or partial response to chemotherapy, they would then receive frontline maintenance therapy with a PARP inhibitor. If the patient had a recurrence that is considered platinum sensitive, they would  receive platinum-based chemotherapy followed by maintenance PARP inhibitor therapy.

Are PARP inhibitors used in low-grade ovarian cancers?
Colleen Bohnenkamp, PharmD, BCOP, BCPS:
All of the trials conducted to date included patients with high-grade serous or endometrioid histology. Low-grade serous ovarian cancers are typically less responsive to chemotherapy compared with high-grade tumors. Hence, hormonal therapies often are used as adjuvant therapy in patients with low-grade serous or endometrioid ovarian cancer. 

Are any of the PARP inhibitors’ starting doses impacted by a patient’s baseline weight or baseline platelet count?
Dane Fritzsche, PharmD, BCOP:
For niraparib, the starting dose requires consideration of patient weight and platelet counts. Based on data from the PRIMA trial, niraparib baseline dosing should be adjusted to 200 mg once daily in patients whose baseline weight is <77 kg or whose baseline platelet count is <150,000/µL. This upfront dose adjustment did not impact efficacy endpoints measured in the trial.

What is your approach to patients missing their medications?
Dane Fritzsche, PharmD, BCOP:
Patient adherence to treatment is always a consideration. If patient adherence to their medication is a concern, my approach is to tease out the reason the dose was missed in the first place. I start by asking patients a few probing questions: Is the patient experiencing adverse events? Is the patient having access issues? Or did the patient simply forget to take their dose? Depending on the answer, I will then attempt to specifically address that issue. For example, if the patient is experiencing adverse events, have they been following all the important supportive care measures, and do they have all the appropriate supportive care medications with them? If a patient reports access issues, such as attempting to extend their dose interval to ameliorate financial concerns, I will explore the patient’s insurance coverage and get our billing coordinators involved to assess whether additional financial assistance is a possibility. Finally, if the patient reports that they had just forgotten that day, I inquire about the methods they use to remember their medications. Perhaps they could benefit from setting alarms with their smart phone, using a dosing calendar, or simply just storing their medication in a more accessible location to act as a memory trigger. I find that these conversations come up frequently in our clinic’s follow-up visits with the pharmacist, underscoring the importance of having numerous patient‒pharmacist touch points. 

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Platelet counts and weight are a consideration when deciding the starting dose for which PARP inhibitor(s)?
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