The Involvement of PARP Inhibitors in the Treatment Landscape for Ovarian Cancer

Video

Ryan Haumschild, PharmD, MS, MBA, opens a discussion surrounding the use of PARP inhibitors within the treatment landscape for ovarian cancer.

Ryan Haumschild, PharmD, MS, MBA: The inhibition of PARP plays an important role in ovarian cancer. Not to get too detailed, but PARP inhibitors block a protein known as the poly (adenosine diphosphate-ribose) polymerase, or PARP. In some cancers, blocking PARP can keep the cells from dividing and replicating. As we know to function and reproduce correctly, the cells in your bodies are constantly copying and proofreading their DNA. When cells detect errors or what we think of as breaks in the DNA, they actively repair those; they fix these errors before copying them again.

There are a few types of DNA-repair machinery that we think about in half of ovarian cancers. It includes those with mutations to the BRCA genes. These cancer cells are defective in 1 type of repair mechanism, but PARP fixes damaged DNA using a different mechanism. This means that when we use PARP inhibitors, we block PARP and can keep the cancer cells from having any type of DNA-repair mechanism, and so they’re not able to copy and multiply. Therefore, healthy cells are largely uninfected by the drug because they have a backup repair mechanism that works. This is what makes PARP inhibitors unique and why they’re so effective in the ovarian space and across some other solid tumors as well.

You have olaparib, rucaparib, and niraparib. They’re unique treatments, but they’re taken differently. When we think about olaparib, we think about 300 mg taken by mouth twice a day. Those come in different tablet formulations when you think about dose reducing. They can be taken with or without food. But keep in mind that with olaparib, you have different cytochrome P450 mechanisms that come into play. You also have different dose modifications. Those different dosing strategies start to separate some of these PARP inhibitors from one another. Other things that come into play are in terms of where they’re indicated. Some might be indicated more in the front line, and some more in the maintenance therapy. As we start to look at some mutational, some might be in HRD mutation, and some might be in BRCA mutation. Many are in all comers depending on the clinical trial data.

One of the first things we always think about, probably across the board, is what are the clinical data? What was the clinical trial, who is studied, and what was the treatment arm? That’s something we home in on. In the PARP inhibitor space, there’s been a lot of innovation across the different therapies. What type of mutation do we need to test for? Is the patient treatment experienced, or are they not? Will they go on maintenance therapy, or will they not? Other things we think about are what type of surgery a patient had, the residual disease, and how that plays into the selection of the PARP inhibitor. What did we see in the clinical trial data? At the end of the day, we also look at those mutations or expressors that I mentioned—BRCA, HRD, and whether a patient is an all comer. Those are some of the differentiations we look at, in addition to adverse effect profiles and the dosing schemes that we talked about.

Transcript edited for clarity.

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