According to Paula Anastasia, RN, MN, AOCN, understanding the role of maintenance PARP inhibitor therapy and the importance of germline testing for all women diagnosed with ovarian cancer are two important areas for oncology nurses .
PARP inhibitor maintenance therapy has been documented to improve progression-free survival (PFS) in women with stage III-IV ovarian cancer after complete response (CR) or partial response (PR) to chemotherapy platinum based. The FDA has approved three agents for the treatment of ovarian cancer: olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula).1 Adverse effects of treatment [AEs] 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] stage 3 [disease], on average, I lived 2 years,” said Anastasia, a gynecologic oncology clinical nurse specialist at UCLA Health. “Now my patients live 5 years, 10 years and more. They may be on long-term intermittent chemotherapy, but there are long-term remissions and breaks in treatment, because we have more and more treatments available. PARP Inhibitors Really Provide PFS [benefit] and with the recent data of olaparib in SOLO-1 [NCT01844986] and ONLY2 [NCT01874353]we are seeing our patients [remain] in first-line maintenance with 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 has been extended with the use of PARP inhibitors and maintenance therapy. We had no maintenance therapy 3 years ago. Now with all these studies we are [in the stage of] adjusting and finding the right dosage and the right concoction for the right patients.”
In an interview with Oncology Nursing News®, Anastasia discussed how multi-panel testing is key to identifying patients who have a germline mutation and are therefore at risk of developing other types of cancer and how personalization of care, such as changing of dose, it is important to determine the appropriate treatments with PARP inhibitors.
Highlight how PARP inhibitor therapies are changing the field.
[There were updates at] the Society of Gynecologic Oncology and ASCO. [These] They were very exciting… but they’re not ready for prime time. There is a lot of new information on combination therapy using PARP inhibitors with the goal of extending the survival benefit for patients.
[Data from] a recent post on the Journal of Clinical Oncologywhich was presented by Bradley J. Monk, MD, at ASCO and that’s the rucaparib study [ATHENA-MONO; NCT03522246], which reviews first-line maintenance therapy, comparing rucaparib with placebo. At this time, there are 2 PARP inhibitors [approved] for first-line maintenance therapy: olaparib and niraparib. Rucaparib is not approved for first line [maintenance] even.
[In ATHENA-MONO] rucaparib showed a median PFS [improvement] in patients who have a 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 being very cautious. Now they say no, that we are not going to give approval until [the data] reach 50% maturity and that may take another 2 years. These data are still premature. [at] 25%. Time is of the essence, but it is also important to have safety data and to look at overall PFS and overall survival as well.
What are some key considerations when selecting a PARP inhibitor for your patient?
Eligibility [for the 2 approved PARP inhibitors] is different depending on whether they have a germ line or a [genomic] tumor mutation. It is important that if patients do not have a germline mutation, they should have their tumors tested for 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 positive germline or HRD tumor have better clinical benefit with a PARP inhibitor.
Niraparib is approved for all stakeholders, whether they have a germline or tumor mutation. That is important to determine a PARP inhibitor and personalized and individualized attention is important to pay attention to the previous adverse events of the patient’s chemotherapy.
As we go forward, after first-line therapy, if patients are in clinical remission or partial remission, which [we expect] 80% of patients will be:[they] you will be offered a PARP inhibitor. Most of the patients who received 1 line of chemotherapy have resistant bone marrow, but there is a percentage that does not, so we want to know how patients did with their first line 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 attention.
What is the nurse’s role in genetic testing and helping patients understand its importance, interpret the results, and help them understand what is going on?
I cannot stress enough that all patients should undergo genetic testing.
When we talk about genetic testing, germline testing, now we want panel testing because in addition to BRCA1 Y BRCA2 pathogenic variants, there are other pathogenic variants in that family [such as] RAD51 Y BRIP1. Sometimes, if clinics are inexperienced in performing genetic testing, these goals may not be achieved. we are lucky [at UCLA] that we have a genetic counselor on site, and I know that each [practice] you don’t have that luxury. Genetic counseling services are available online, and in addition to testing, all patients should also receive counseling. [and the opportunity] to ask what does this information mean?
If a patient has a germline mutation, there are other cancer risks: breast cancer, pancreatic cancer, melanoma, etc. Also, 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 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 to let them know that this is part of the standard of care.
The other thing we don’t talk about enough is health care disparities. There is so much data out there and not all ethnic groups are getting genetic testing. We do our patients a disservice if we don’t test, because then they may be missing out on receiving a PARP inhibitor as maintenance therapy or in a recurrent setting. Not only is this a hurdle for the patient, but we’re also not cascading testing on their family members and thus preventing cancer for them as well.
[We also need to be] aware of our own practices and inspire confidence in our patients because we want the 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 be experiencing toxicities with continued treatment?
I always tell my nurses… you may not be an expert in knowing the dosages. That’s what the prospects are for, that’s what the pharmacist is for. In my practice we only do oncology, so I’m very attuned to medications and dosages.
Looking at [data from studies of] niraparib, patients weighing less than 77 kg and/or have platelets [counts] less than 150,000, you should start with 200 mg daily, as opposed to the FDA-approved dose of 300 mg. me [was involved in] original studies and observed tremendous grade 4 thrombocytopenia when these patients received the 300 mg dose. It was almost counterintuitive because we had delays in dosing and patients couldn’t get the therapeutic drug on time.
I remind patients that there may be times when we review their [complete blood count] CBC every week when we first started niraparib. If they’re taking olaparib, we review it monthly. The objective is to see its tolerability and we are looking for hematological changes. I remind patients that when they have [intravenous] IV therapy, we base those doses on your height and weight, but with oral medications, it’s one size fits all. If we need to delay or reduce the dose, again, that’s [based on] your body’s metabolism. I remind you that we are individualizing and personalizing your care.
What AAs should patients look for when taking a PARP inhibitor?
With front line maintenance, patients do much better and communication is key.
The classic effects are fatigue, nausea, and then hematologic AEs. We monitor hematology AEs and that’s why we really require that they have their lab work. [more frequently at the start] so we can modify things. Patients will notice fatigue and 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.
The nausea is more like underlying nausea, and I tell patients to take an anti-nausea medication at bedtime, just to see if we can mitigate it.
Are there any patients who are not a good candidate for PARP inhibitors, even when it is the standard of care?
I think most patients are suitable for PARP inhibitors; however, sometimes we need to start with a lower dose. Just because we start at a lower dose doesn’t mean it’s going to be sub-therapeutic. [It’s important to consider] whether the patient can take oral medications [and if] they will be adherent.
There may also be patients with poor performance status and comorbidities. There is a very small percentage of patients for whom [PARP inhibitors] might not be the right one. But for most, paying attention to individual AE profiles, response to chemotherapy, and whether they benefit from having a lower dose than the FDA-approved starting dose [are important considerations].
What kinds of conversations should occur between patients and providers before starting these therapies?
One thing we don’t talk about is financials. [burden]. These drugs can be very expensive and I have [seen] $0 copays and I [seen] copays from $5,000 to $10,000. There are copay assistance programs and I don’t think we use them enough, but I’ve been able to get grants for patients and pharmaceutical companies have been very helpful.
Sometimes it can take a long time, but copay assistance programs and access groups will do some of the legwork for us.
Reference
Pthuri B, O’Cearbhaill R, Eskander R, Armstrong D. First-line PARP inhibitor maintenance therapy in ovarian cancer: a practice statement from the Society for Gynecologic Oncology. Gyncol Oncolo. 2020;159(1):8-12. doi:10.1016/j.ygyno.2020.07.097