Patient Selection and PARP Inhibitors in Ovarian Cancer

Robert L. Coleman, MD: We’re really excited to have 3, or maybe even 4 options for patients in the PARP inhibitor drug class. It’s important because these drugs, from an efficacy standpoint, all seem to be pointing in the same direction in confirming the overall efficacy. There are definite patient characteristics that interact with these specific drugs. The side effects that some of them experience will help us, in the future, to identify how we can narrow in on that selection. But, we need the menu so that we can actually deal with patients’ questions.

For patients that have difficulty taking pills, once-a-day might be good. For patients that have problems with bone marrow, a drug that doesn’t have a lot of bone marrow toxicity, that can be modulated in an easier way, may be an option. Some people have more nausea because these drugs are metabolized in a slightly different way. Some patients experience higher degrees, or see more effects on their creatinine values, even though they may have normal creatinine clearance. These are subtleties that come up on all of the trials that we’ve done for patients who receive the drugs. The most important thing that we’d like to get to is having these drugs administered daily, because they have short half-lives. It’s critical that patients stay on them and not take breaks. And so, sometimes retooling the drugs, changing them, or making them optimized to the patient is the best option in gaining the most benefit out of the drug for the long-term.

We’re excited because the work that’s come from the single-agent experience with PARP inhibitors has allowed us to dig deep into DNA damage response pathways. Now, we’ve identified a number of new potential targets to further move this drug along.

When identifying the types of patients that are best going to respond to a single agent versus a combination therapy, what do we do in a patient who has a recurrence and becomes resistant to the therapy? Can we use it, the treatment, again in the future? Coming up with a dynamic tool to sort that out is really the next major discovery that we’ll need to see in the treatment of patients with ovarian cancer. The opportunity to leverage this specific aspect into additional therapies that will either be in combination or in response to a sequence has really set off a lot of investigative energy, as we move forward.
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