PARP Inhibitors for Second-Line Maintenance in Ovarian Cancer

EP: 1.A History of PARP Inhibitors

EP: 2.Mechanism of Action and Efficacy of PARP Inhibitors in Ovarian Cancer

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EP: 3.PARP Inhibitors for Second-Line Maintenance in Ovarian Cancer

EP: 4.Patient Eligibility for the Use of PARP Inhibitors in Ovarian Cancer

EP: 5.ARIEL3 Trial: Exploratory Analysis Data

EP: 6.Monitoring PARP Inhibitors in Ovarian Cancer for Toxicities

EP: 7.Ongoing Research With PARP Inhibitors in Ovarian Cancer

EP: 8.Second-Line Maintenance Challenges for PARP Inhibitors in Ovarian Cancer

Bhavesh Shah, RPh, BCOP: We understand the mechanism and the rationale for using PARP inhibitors specifically in the second line, and we talk about the residual disease. What is the knowledge of where these agents fit into the second-line maintenance setting? Thomasina, if you can help us to understand why we use them. We know there is residual disease, but there’s other benefit; what is that and why? How do we use these agents in second-line maintenance?

Thomasina Morris, RPh, MHA, BCOP: The good part is that a lot of patients with ovarian cancer will come in and do cytoreductive surgery and then chemotherapy. Like you said, Taxol is one, but carboplatin is the other. We then determine if these patients are platinum-sensitive versus platinum-resistant. If they are sensitive, they’ll have a recurrence out 12 months or more. If they are resistant, they’ll have a recurrence much sooner. When we look at these patients, we want to see when they recur. Like you said, it’s a good 80% of patients who can recur after having initial treatment. After their 6 cycles of Taxol/CARBO [carboplatin] or paclitaxel/carboplatin, they go on surveillance, or they go on Avastin [bevacizumab] maintenance. A lot of these patients will not come back to us for a couple of months, maybe for scans, laboratory work, etc.

The providers are now doing more molecular testing on the tumor for the somatic BRCA mutation and also germline; when we find that they’re platinum-sensitive, we’re now looking at these patients who could fit a PARP inhibitor. They’re having platinum sensitivity, plus they’re also BRCA mutated. Right there gives you the opportunity to say these patients will have a better progression-free survival if they are given a PARP inhibitor. If that’s the case, how do we get these patients to be compliant with an oral medication? The last thing they had was an IV [intravenous] medication; they think, “I’ve got a pill, I can just go home and take this every day, this is great,” and it doesn’t work that way.

Bhavesh Shah, RPh, BCOP: Thomasina, can you define for our audience what platinum-sensitive and platinum-refractory means?

Thomasina Morris, RPh, MHA, BCOP: Platinum-sensitive technically is when we give paclitaxel/carboplatin and we see patients respond, such as by CA-125 [cancer antigen 125] going down, and since they went through surgical debulking, you want to make sure that there’s nothing else coming up on the scan. These patients will come back to the clinic every 3 months, every 6 months, to be reevaluated. During that time, your hope is they don’t have a recurrence. That means that the paclitaxel/carboplatin has done its job; it’s worked to keep this disease at bay. By 12 months is usually our marker when we say, “Well, have they recurred?” In some cases, they have not. However, if they do, then we start talking about second options. Usually, the window is about 6 months when we see refractory disease or relapse. That tells us that the carboplatin and paclitaxel didn’t work as well.

We must get rid of the carboplatin and give the patient another treatment because we realize now they’re not carboplatin-sensitive or platinum-sensitive. In that scenario, you start playing with different medications to see what you can do to get them to a point of getting response. That response is what you’re going for, whether it’s the CA-125 or patients having ascites and having discomfort. Does that take away from a lot of that when we give these medications? With bevacizumab, we can give it regardless of molecular profile; we can put it into a patient’s regimen at any time. We’ve been able to have advancements just with bevacizumab. Now with the PARP inhibitors on board, it makes it a lot easier for providers. An example today was a patient who was on liposomal doxorubicin and carboplatin, and progressed. The doctor turned around and said she’s platinum-sensitive, she’s BRCA positive, we already did the HRD [homologous recombination deficiency] test that gets done to determine response to PARP inhibitors, and she was going to be put on to a [PARP inhibitor]. That is the kind of decision that was just made today in that category of how you determine PARP inhibitors for patients with ovarian cancer that has recurred.

This transcript has been edited for clarity.