Nurses Play Key Role in Facilitating Maintenance Therapy With PARP Inhibitors in Ovarian Cancer

Paula Anastasia, RN, MN, AOCN

Understanding the role of maintenance PARP inhibitor therapy and the importance of germline testing for all women with a diagnosis of ovarian cancer are 2 areas of importance 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 approved by the FDA for the treatment of ovarian cancer: olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula).¹ Treatment adverse effects [AEs] of anemia, nausea, and other hematological effects should be monitored with continued communication between patients and nurses.

“When I started [nursing] 30 years ago, my patients who [had] stage 3 [disease], on average, lived 2 years,” said Anastasia, a gynecologic Oncology Clinical Nurse Specialist for UCLA Health. “Now my patients are living 5 years, 10 years, and longer. They may be on chemotherapy on and off for the long term, but there are long-term remissions and treatment breaks, because we have more and more treatments available. The PARP inhibitors are really providing PFS [benefit] and with the recent data from olaparib in SOLO-1 [NCT01844986] and SOLO2 [NCT01874353], we are seeing our patients [remain] on frontline maintenance olaparib post chemotherapy [and are] disease free for 3 to 5 years.”

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

In an interview with Oncology Nursing News®, Anastasia discussed how multipanel testing is key for identifying patients who have a germline mutation and are therefore at risk of developing other cancers and how customization of care, such as changing of dosing, is importance in determining appropriate PARP inhibitor treatments.

Please highlight how PARP inhibitor therapies are changing the field?

[There were updates at] the Society of Gynecologic Oncology and at ASCO. [These] were very exciting…but they’re not ready for primetime. There’s a lot of new information with combination therapy using PARP inhibitors with the goal to extend survival benefit for patients.

The rucaparib study [ATHENA-MONO; NCT03522246], is looking at frontline maintenance therapy, comparing rucaparib with placebo. Right now, there are 2 PARP inhibitors [approved] for frontline maintenance therapy—olaparib and niraparib. Rucaparib is not approved for frontline [maintenance] yet.

[In ATHENA-MONO] rucaparib showed a median PFS [improvement] in patients who have a homologous recombinant–deficiency [HRD] compared with placebo. [The study] was talked about, saying [it would support] a new FDA indication, but fortunately, or unfortunately, the FDA is being very cautious. They are now saying no, we’re not going to provide approval until [the data] reach 50% maturity and that can take another 2 years. These data are still premature [at] 25%. Time is of essence, but it’s also important to have safety data and look at overall PFS and then in addition, overall survival.

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

Eligibility [for the 2 approved PARP inhibitors] is different based on whether they have a germline or a [genomic] tumor mutation. It’s important that if patients don’t have a germline mutation, they should have tumor testing to see if there’s a deficiency in the homologous recombination pathway. If patients have a deficiency, they would be eligible for a PARP inhibitor, [and studies have shown that] patients who have a germline or an HRD-positive tumor have a better clinical benefit with a PARP inhibitor.

Niraparib is approved for all comers, whether they have a germline or tumor mutation. That’s important in determining a PARP inhibitor and personalized and individualized care is important to pay attention to the patient’s prior AEs from chemotherapy.

As we go forward, after frontline therapy, if patients are in a clinical remission or partial remission—which [we expect] 80% of patients will be—[they] will be offered a PARP inhibitor. Most patients who received 1 line of chemotherapy have sturdy bone marrow, but there is a percentage who don’t, so we want to know, how did patients do with their frontline therapy? Did they require growth factors? Were there dose reductions? Do they have a history of hypertension, which may indicate whether they would tolerate niraparib? All those questions personalize care.

What is the nurse’s role in genetic testing and helping patients understand the importance of it, interpreting results, and helping them make sense of what's going on?

I can't emphasize enough that all patients should have genetic testing.

When we talk about genetic testing, germline testing, now we want 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 aren’t experienced in doing genetic testing, then these targets may be missed. We’re fortunate [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 counselor services and in addition to testing, all patients should also have counseling [and the opportunity] to ask what does this information mean?

If a patient carries a germline mutation there are other cancer risks: breast cancer, pancreatic cancer, melanoma, etc. In addition, if we’ve 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 a very good thing. I think a lot of that is very helpful and there are support groups, for patients who have germline mutations. I think part of our role as nurses is letting them know that this is part of standard of care.

The other thing that we don’t talk enough about is health care disparities. There is so much data out there and not all ethnic groups are having genetic testing. We do a disservice to our patients if we’re not testing, because then they may be missing out on receiving a PARP inhibitor as a maintenance therapy, or in a recurrent setting. Not only is it a hindrance to the patient, but we’re also not doing cascade testing on their family members, and therefore preventing cancers for them as well.

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

What data are available surrounding tolerability and dose changes for patients receiving PARP therapy? What have you found useful in helping patients who may be experiencing toxicities with continued treatment?

I always tell my nurses…you may not be an expert on knowing the doses. That’s what the package inserts are for, that’s what the pharmacist is for.

Looking at [data from studies of] niraparib, patients who weighed less than 77 kg and/or have platelet [counts] less than 150,000, should be started at 200 mg daily, as opposed to FDA-approved dose, which is 300 mg. I [was involved in] the original studies and saw a tremendous grade 4 thrombocytopenia when these patients were receiving the 300-mg dose. It was almost counterintuitive because we had dose delays and patients couldn’t receive the therapeutic drug on time.

We check their [complete blood count] CBC every week when we first start niraparib. If they’re on olaparib, we check it monthly. The goal is to see their tolerability; we are looking for any hematological changes.

I remind patients that when they get [intravenous] IV therapy, we are basing those doses on their height and weight, but with oral medications, it’s one size fit all. If we need delay or dose reduce, again, that’s [based on] their body’s metabolism. I remind them that we are individualizing and personalizing their care.

What AEs should patients be looking for when they’re on a PARP inhibitor?

With the first line maintenance patients do so much better and communication is key.

The classic effects are fatigue, nausea, and then hematological AEs. We oversee the hematological AEs and that’s why we really mandate that they have their labs drawn [more frequently at the start] so we can tweak things.

Nausea is more like underlying queasiness, and I tell patients to take an antinausea medicine at bedtime, just to see if we can mitigate [it].

Are there any patients who may not be a good fit for PARP inhibitors, even when it is standard of care?

I think most patients are fit to have PARP inhibitors; however, sometimes we must start at a lower dose. Just because we’re starting at a lower dose does not mean it’s going to be sub therapeutic. [It’s important to consider] if the patient is able to take oral medications [and if] they are going to be adherent.

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

What kind of conversations need to happen between patients and providers before starting these therapies?

Something we don’t talk about is the financial [burden]. These medications can be very expensive, and I’ve [seen] copays of $0 and I’ve [seen] copays of $5000 to $10,000. There are copay assistance programs, and I don't think we utilize them enough, but I’ve been able to get grants for patients and the pharmaceutical companies have been very helpful.

It can sometimes be time consuming, but the copay assistance programs, and access groups will do some of the legwork for us.

Reference

Pthuri B, O’Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: a Society of Gynecologic Oncology practice statement. Gynecol Oncol. 2020;159(1):8-12. doi:10.1016/j.ygyno.2020.07.097