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Ongoing PARP Trials in Recurrent Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, Arizona Oncology Practice of US Oncology; Oliver Dorigo, MD, PhD, Stanford University Medical Center; Thomas Herzog, MD, University of Cincinnati Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center; Leslie M. Randall, MD, MAS, University of California, Irvine
Published: Thursday, Sep 20, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s talk about some of the ongoing clinical trials with PARP inhibitors. It’s a very exciting time in recurrent ovarian cancer. We talked about moving PARP inhibitors into the frontline setting. There is SOLO-1 with olaparib, PRIMA with niraparib, and the combination of bevacizumab and olaparib in PAOLA-1.
But in recurrent disease, we have a second opportunity, other than maintenance—treatment. At the 2018 ASCO Annual Meeting, Katie, you presented a wonderful study called QUADRA. Tell us about QUADRA. What were the key findings?

Kathleen Moore, MD: QUADRA is a really unique trial. It’s actually the biggest PARP treatment trial run—463 patients. The primary outcome of this trial was to look at the overall response rate of niraparib in patients who were in their fourth or fifth line of treatment, who were still considered sensitive to platinum—not meaning that they had gotten platinum as their last line, but they were still considered sensitive to platinum—and were HRD-positive. That was the primary group.

In this relatively heavily pretreated group of patients, the overall response rate was 29%. If you included those patients who were in a sixth-, seventh-, or eighth-line setting, or whatever, it was 27%. So, you actually didn’t lose a whole lot of efficacy. Of the BRCA patients who were enrolled, regardless of platinum sensitivity, for those who responded, the duration of response was almost 10 months. In the HRD-positive group, it was 8.4 months. This is one of the first big trials, outside of phase I expansion cohorts, to look at the efficacy of PARP inhibition in patients who had been very heavily pretreated. For that reason, it’s a very unique and exciting trial. It speaks to the benefit of PARP inhibitors. In an area where we talk about using PARP inhibitors early, which may be true, they are still active later on.

Bradley J. Monk, MD, FACS, FACOG: In this 460-patient trial, I’m struck by the fact that it confirms our knowledge of what the predictors of PARP sensitivity are. When you start to fill out those boxes—molecular signature, platinum sensitivity, and number of lines of therapy—you kind of get a sense that this would be impactful. And at the lower end of the spectrum, it’s about 10%. Ten percent isn’t great, but some of those patients have durable responses. In the better population, maybe those who are in their fourth or fifth line of therapy, who are HRD-positive, it’s 30%.

Kathleen Moore, MD: Right.

Bradley J. Monk, MD, FACS, FACOG: It really reinforces our understanding of the biology of this. So, congratulations.

Kathleen Moore, MD: Thank you.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s talk about some of the ongoing clinical trials with PARP inhibitors. It’s a very exciting time in recurrent ovarian cancer. We talked about moving PARP inhibitors into the frontline setting. There is SOLO-1 with olaparib, PRIMA with niraparib, and the combination of bevacizumab and olaparib in PAOLA-1.
But in recurrent disease, we have a second opportunity, other than maintenance—treatment. At the 2018 ASCO Annual Meeting, Katie, you presented a wonderful study called QUADRA. Tell us about QUADRA. What were the key findings?

Kathleen Moore, MD: QUADRA is a really unique trial. It’s actually the biggest PARP treatment trial run—463 patients. The primary outcome of this trial was to look at the overall response rate of niraparib in patients who were in their fourth or fifth line of treatment, who were still considered sensitive to platinum—not meaning that they had gotten platinum as their last line, but they were still considered sensitive to platinum—and were HRD-positive. That was the primary group.

In this relatively heavily pretreated group of patients, the overall response rate was 29%. If you included those patients who were in a sixth-, seventh-, or eighth-line setting, or whatever, it was 27%. So, you actually didn’t lose a whole lot of efficacy. Of the BRCA patients who were enrolled, regardless of platinum sensitivity, for those who responded, the duration of response was almost 10 months. In the HRD-positive group, it was 8.4 months. This is one of the first big trials, outside of phase I expansion cohorts, to look at the efficacy of PARP inhibition in patients who had been very heavily pretreated. For that reason, it’s a very unique and exciting trial. It speaks to the benefit of PARP inhibitors. In an area where we talk about using PARP inhibitors early, which may be true, they are still active later on.

Bradley J. Monk, MD, FACS, FACOG: In this 460-patient trial, I’m struck by the fact that it confirms our knowledge of what the predictors of PARP sensitivity are. When you start to fill out those boxes—molecular signature, platinum sensitivity, and number of lines of therapy—you kind of get a sense that this would be impactful. And at the lower end of the spectrum, it’s about 10%. Ten percent isn’t great, but some of those patients have durable responses. In the better population, maybe those who are in their fourth or fifth line of therapy, who are HRD-positive, it’s 30%.

Kathleen Moore, MD: Right.

Bradley J. Monk, MD, FACS, FACOG: It really reinforces our understanding of the biology of this. So, congratulations.

Kathleen Moore, MD: Thank you.

Transcript Edited for Clarity 
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