Nurses play a key role in facilitating maintenance therapy with PARP inhibitors in ovarian cancer

Understanding the role of maintenance therapy with PARP inhibitors and the importance of germline testing for all women diagnosed with ovarian cancer are two areas of interest for oncology nurses, according to Paula Anastasia, RN, MN, AOCN.

Maintenance therapy with PARP inhibitors has been documented to improve progression-free survival (PFS) in women with stage III-IV ovarian cancer following a complete response (CR) or partial response (PR) to platinum-based chemotherapy. Three agents are FDA-approved for the treatment of ovarian cancer: olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula).1 Treatment side effects [AEs] of anemia, nausea and other hematologic effects should be monitored with ongoing communication between patients and nurses.

“When I started [nursing] 30 years ago, my patients who… [had] phase 3 [disease]lived an average of 2 years,” said Anastasia, a gynecologic oncology clinical nurse practitioner for UCLA Health. “Now my patients live 5 years, 10 years and more. They can be on and off chemotherapy for the long term, but there are long-term remissions and treatment breaks as we have more and more treatments available. The PARP inhibitors really take care of PFS [benefit] and with the recent data of olaparib in SOLO-1 [NCT01844986] and SOLO2 [NCT01874353]we see our patients [remain] about first-line maintenance olaparib after chemotherapy [and are] disease free for 3 to 5 years.”

Anastasia added that there is still a long way to go to define the role of PARP inhibitors. “Long-term survival is increased with the use of PARP inhibitors and maintenance therapy. We didn’t have maintenance therapy 3 years ago. Now with all these studies we are [in the stage of] tweaking and finding the right dose and brew for the right patients.”

In an interview with Oncology Nursing News®, Anastasia discussed how multipanel testing is essential for identifying patients with a germline mutation and therefore at risk of developing other cancers and how adapting care, such as changing the dose, is important in determining suitable PARP inhibitors.

Can you point out how therapies with PARP inhibitors are changing the field?

[There were updates at] the Society for Gynecological Oncology and at ASCO. [These] were very exciting…but they are not ready for primetime yet. There is a lot of new information about combination therapy with PARP inhibitors with the aim of increasing the survival benefit for patients.

[Data from] a recent publication in the Journal of Clinical Oncologythat was presented by Bradley J. Monk, MD, at ASCO and that is the rucaparib study [ATHENA-MONO; NCT03522246], which looks at first-line maintenance therapy, comparing rucaparib with placebo. There are currently 2 PARP inhibitors [approved] for first-line maintenance therapy – olaparib and niraparib. Rucaparib is not approved for front line [maintenance] yet.

[In ATHENA-MONO] rucaparib showed a median PFS [improvement] in patients with homologous recombinant deficiency [HRD] compared to placebo. [The study] was spoken, saying: [it would support] a new FDA indication, but fortunately, or unfortunately, the FDA is very cautious. They say no now, we don’t approve [the data] Reach 50% maturity and that can take another 2 years. This data is still premature [at] 25%. Time is of the essence, but it is also important to have safety data and look at overall PFS and then overall survival.

What are some important considerations when selecting a PARP inhibitor for your patient?

Suitability [for the 2 approved PARP inhibitors] differs according to whether they have a germline or a [genomic] tumor mutation. Importantly, if patients do not have a germline mutation, they should undergo tumor testing to see if there is a deficiency in the homologous recombination pathway. If patients have a deficiency, they are eligible for a PARP inhibitor, [and studies have shown that] patients with a germline or HRD positive tumor have a better clinical benefit with a PARP inhibitor.

Niraparib is approved for all newcomers, whether they have a germline or tumor mutation. That is important in determining a PARP inhibitor and personalized and individualized care is important to pay attention to the patient’s previous side effects of chemotherapy.

As we move forward, after first-line therapy when patients are in clinical or partial remission, what: [we expect] 80% of patients will—[they] you will be offered a PARP inhibitor. Most patients who have received 1 line of chemotherapy have solid bone marrow, but there is a percentage that do not, so we want to know how the patients did with their first line therapy? Did they need growth factors? Were there dose reductions? Do they have a history of hypertension, which may indicate whether they would tolerate niraparib? All these questions make care personal.

What is the nurse’s role in genetic testing and helping patients understand its importance, interpreting results and helping them understand what is going on?

I cannot emphasize enough that all patients should undergo genetic testing.

When we talk about genetic testing, germline testing, now we want to do panel testing because in addition to the BRCA1 and BRCA2 pathogenic variants, there are other pathogenic variants in that family [such as] RAD51 and BRIP1. Sometimes, if clinics are not experienced in doing genetic testing, these targets can be missed. we are lucky [at UCLA] that we have a genetic counselor on site, and I know that every… [practice] does not have that luxury. There are online genetic counseling services and in addition to testing, all patients should also receive counseling [and the opportunity] to ask what this information means?

If a patient carries a germline mutation, there are other cancer risks: breast cancer, pancreatic cancer, melanoma, etc. In addition, if we have identified a germline mutation in our patients, we want to do cascade or family testing – siblings, parents, aunts, uncles, cousins. If we can help prevent cancer by testing a family member, we’ve done something really good. I think a lot of that is very helpful and there are support groups for patients with germline mutations. I think part of our role as nurses is to let them know that this is part of standard care.

The other thing we don’t talk about enough is health inequalities. There is so much data and not all ethnic groups undergo genetic testing. We are doing our patients a disservice if we don’t test, as they may miss out on a PARP inhibitor as maintenance therapy or in a recurring setting. Not only is it a barrier to the patient, but we don’t do cascade testing on their relatives, which is why we prevent cancer for them as well.

[We also need to be] aware of our own practices and inspire confidence in our patients because we want what is best for them [and we must discover] what is important to the patient.

What data are available on tolerability and dose changes for patients receiving PARP therapy? What have you found helpful in helping patients who may experience toxicity with continued treatment?

I always tell my nurses… you may not be an expert in knowing the doses. That’s what the package inserts are for, that’s what the pharmacist is for. In my practice we only do oncology and so I am very aware of the medicines and the dosages.

Watch [data from studies of] niraparib, patients who weighed less than 77 kg and/or have platelets [counts] less than 150,000, should be started at 200 mg per day, as opposed to the FDA-approved dose, which is 300 mg. l [was involved in] the original studies and saw massive Grade 4 thrombocytopenia when these patients received the 300 mg dose. It was almost counterintuitive because we had dose delays and patients couldn’t get the therapeutic drug on time.

I remind patients that there are times when we [complete blood count] CBC every week when we first start niraparib. If they use olaparib, we check it monthly. The goal is to see their tolerability and we look for any haematological changes. I remind patients that when they… [intravenous] IV therapy, we base those doses on their height and weight, but with oral medication, it’s one size fits all. If we need a delay or dose reduction, again, that is [based on] their body’s metabolism. I remind them that we individualize and personalize their care.

What side effects should patients be aware of when taking a PARP inhibitor?

With primary care, patients do so much better and communication is key.

The classic effects are fatigue, nausea and subsequent haematological side effects. We oversee the haematological AEs and so we really require them to get their labs signed [more frequently at the start] so we can adjust things. Patients will notice fatigue and this is usually[would when] patients had 3, 4 or 5 prior lines of therapy and a PARP inhibitor and poor bone marrow reserve and were exhausted.

Nausea is more like underlying nausea, and I tell patients to take an anti-nausea medicine at bedtime just to see if we can ease it.

Are there any patients who may not be suitable for PARP inhibitors, even if it is standard of care?

I think most patients are fit to have PARP inhibitors; however, sometimes we need to start with a lower dose. Just because we start with a lower dose doesn’t mean it will be subtherapeutic. [It’s important to consider] if the patient can take oral medication [and if] they will be pending.

There may also be patients with poor performance status and comorbidities. There is a very small percentage of patients for whom [PARP inhibitors] may not be the right fit. But for the majority, attention to individual AE profiles, chemotherapy response, and whether they benefit from a lower dose than the FDA-approved starting dose [are important considerations].

What kind of conversations should take place between patients and healthcare providers before starting these therapies?

Something we don’t talk about is the financial [burden]. These drugs can be very expensive, and I have [seen] $0 copays and I have [seen] copays from $5,000 to $10,000. There are copay utilities and I don’t think we use them enough, but I’ve been able to get grants for patients and the drug companies have been very helpful.

It can be time consuming at times, but the copay tools and access groups will do some of the work for us.

Reference

Pthuri B, O’Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: a statement of practice from the Society of Gynecologic Oncology. Gynaecol Oncol. 2020;159(1):8-12. doi:10.1016/j.ygyno.200.07.097

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