PARP Inhibition Continues to Make Waves in Ovarian Cancer

Terry L. Evans, MD

PARP inhibitors can be helpful therapeutic tools in prolonging the time between chemotherapy treatments in patients with ovarian cancer who are in their third line of therapy or beyond, explained Terry L. Evans, MD.

However, Evans also explained that PARP inhibitors still need to be better understood in determining who is most optimal to receive them, and who should receive them in combination with other agents.

“I'm a big fan of PARP inhibitors; I'm just not sure we all understand the nuances necessary to put a patient on [this class of drugs],” said Evans, a clinical assistant professor at the University of Pittsburgh School of Medicine and medical director of the Hillman Cancer Center, Arnold Palmer Pavilion.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Evans discussed the use of PARP inhibitors in ovarian cancer and how they are poised to optimally fit in the treatment paradigm.

OncLive: How are PARP inhibitors defined in the treatment paradigm of ovarian cancer?

Evans: PARP inhibitors have the potential to revolutionize our treatment of patients with ovarian cancer. I'm old enough to remember the old-fashioned CAP chemotherapy program, which comprised cyclophosphamide, doxorubicin, and cisplatin. This was likely used until the 1980s.

When patients had recurrences of ovarian cancer, as they almost always do, most of us in the community have just gone from one chemotherapy to another chemotherapy and so on. Every time you have to go to another [chemotherapy], especially after the third-line setting, it's a matter of diminishing returns. If you're lucky enough to get a response, it does not last very long. I see PARP inhibitors coming into play in the later stage of disease, if one is considering giving chemotherapy in the fourth-, fifth-, or sixth-line setting. At that point, you're really talking about palliation of symptoms and trying to keep the patient out of the hospital and focus more on quality of life. That's where I see the potential for PARP inhibitors going forward, as being the biggest contributor to some progress we're making.

What challenges do you typically observe with PARP inhibitors?

A lot of my colleagues are not well-versed in some of the molecular aspects of these drugs. Everybody knows about BRCA1/2, but not everybody knows about homologous recombination, the other part of this pathway that may allow more patients to participate in these drugs. If a patient has a BRCA1/2 mutation or some other manifestation of homologous recombination deficiency (HRD), they should be put on maintenance therapy. That is a separate issue from treatment.

Where do you see future research heading in this area?

Activity of the PARP inhibitors is pretty well understood when used as single agents. The future is looking at combinations with drugs, such as bevacizumab (Avastin), and some of the checkpoint inhibitors. Some data suggest there may be synergy with these combinations. At the end of the day, it's going to boil down to some element of insurance coverage and financial toxicity to the patients.

From my perspective, [insurance coverage] is a big deal. That's one of the bigger [challenges] in dealing with these drugs in our center. For example, we have people who do nothing other than try to get help for patients and their families for these drugs. I know how much each of these drugs cost per day. You have to use them judiciously and try to get help for the patients’ families.

Curative drugs are a different story, but these are not curative drugs. They prolong progression-free survival and they are an option to chemotherapy going forward. When you're out to the fourth-, fifth-, or sixth-line setting, that's where they potentially have the greatest role going forward in treating this disease.

What is your advice to your colleagues when they are navigating with financial toxicity and whether they should administer certain agents?

I would say my advice is to learn one of the drugs; learn how to use it and find out how much it costs. If one assumes that all 3 of these drugs are equal, and my opinion is that they are, cost is a big factor once you get past efficacy and toxicity. That is how I would approach it.

Additionally, since clinical trials are the number one priority [for all of us], a lot of clinical trials get the drugs paid for by some other mechanism. I would encourage all of my colleagues to participate in good clinical trials.

What is your take-home message for your colleagues treating patients with ovarian cancer?

When you look at the treatments we have had for ovarian cancer over the last 20 or 30 years, there hasn't been a lot of progress made outside of chemotherapy. The angiogenesis inhibitors have come into play, but PARP inhibitors are going to be a better option than bevacizumab. We're going to be asking our colleagues to look critically at the data, pick the drug that's the most cost effective, learn about HRD, what tests to order, and then put patients on maintenance therapy after your second-line therapy. Then, start thinking about how you're going to use these in sequence. There's no data in [sequential use of] PARP inhibitors; If patients receive have one PARP inhibitor and then progress, there are no data on using a different PARP drug yet. It is just a matter of familiarity for clinicians who take care of patients, more than anything else.