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Angela Jain, MD, provides perspective on use of PARP inhibitors in the treatment of patients with advanced ovarian cancer.
To stay on top of 2 of the most common adverse effects (AEs) of PARP inhibitors in advanced ovarian cancer—cytopenias and fatigue—patients should undergo weekly monitoring of their blood counts and increase their physical activity, according to Angela Jain, MD.
“Common AEs of PARP inhibitors include cytopenias, like neutropenia, anemia, and thrombocytopenia. [Also], fighting fatigue can be quite difficult for some patients, but I recommend something that’s maybe counterintuitive: trying to increase physical activity and strength training, as I find that many patients have lost some stamina after surgery and chemotherapy,” said Jain.
In an interview with OncLive®, Jain, an assistant professor in the Department of Hematology/ Oncology at Fox Chase Cancer Center, provided perspective on the use of PARP inhibitors in the treatment of patients with advanced ovarian cancer.
Jain: The use of PARP inhibitors in frontline maintenance therapy is relatively new, but several great trials show that there are some opportunities for this [class of agents].
Patients with a germline or somatic BRCA mutation do benefit from PARP maintenance therapy, [specifically with] the combination of olaparib [Lynparza] and bevacizumab [Avastin]. Olaparib plus bevacizumab is given for 2 years after initial chemotherapy and surgery. Bevacizumab is also usually started at the time of treatment during that paradigm, and then olaparib is added as maintenance after it’s all over. Niraparib [Zejula] has been given an indication for frontline maintenance regardless of a BRCA mutation, which has really changed how we think about maintenance therapy for all our patients with ovarian cancer.
[Excellent] guidelines have been set in terms of dosing the PARP inhibitors. Usually, I try to start patients at their full recommended dose unless there is a good reason not to, because that is the most effective dose. Niraparib has a “weights and plates” dosing, so if a patient’s weight is under 150 pounds, or their platelet count is under 150,000 at the time of starting therapy, [you can] reduce the dose at the start of therapy to 200 mg to reduce the chances of cytopenias, but otherwise, there is no other recommendation at the start of therapy to dose reduce.
Some patients will talk about having some nausea [and/or] fatigue with the PARP inhibitors. I make sure that patients have antiemetics at home in case they’re needed. [We also have to] monitor blood counts. I usually monitor them weekly for the first month or two to look out for those changes, then make dose modifications as necessary. Patients also have to work at rebuilding the stamina [they lost after surgery and chemotherapy]. Plus, with niraparib, you do have to worry about patients developing some hypertension and headaches. That’s something to look out for and monitor a little bit more closely as well at home.
This will [likely] be the first time that patients are on an oral [cancer] therapy. Some patients may assume that these drugs don’t have AEs that need to be monitored, but I do recommend, for the first month or two, scheduling an every-other-week phone call or office visit to confirm that they’re tolerating the medication well. This can help look out for cytopenias and hypertension, and it reminds patients that AEs [are possible] and that they should call if they’re having any trouble.
PARP inhibitors are now approved in multiple settings: We can treat patients in the frontline maintenance setting; in the second-line, platinum-sensitive setting; and in the recurrent setting, for patients with a BRCA mutation or [homologous recombination deficiency]–positive loss of heterozygosity. Being cognizant of potential AEs and potentially thinking about when we would want to use a PARP inhibitor in those settings is [key], especially considering that there is a rare risk of leukemia and [myelodysplastic syndrome] in the future. Giving thought to when to use these drugs can sometimes be a little tricky, and having that honest conversation with our patients is important.
We reuse platinum with recurrence, and we have to ask if we can reuse PARP inhibitors. If we have a patient who can receive a PARP inhibitor as frontline maintenance, should we use it again in second-line maintenance? The OReO study looked at that question and found a progression-free survival benefit, regardless of a BRCA mutation, for rechallenge with a PARP inhibitor. Other studies are coming, but it is promising that we can still hold this option again for patients if the setting is right.
The space of PARP inhibitors in ovarian cancer is still very much evolving, especially as newer therapies arise or [are being combined] with older therapies. We know that there might be benefits in combining [PARP inhibitors] with bevacizumab [or] with immunotherapy. These trials are ongoing and I’m looking forward to their results [in the future].