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Maintenance Therapy in Ovarian Cancer: PARP Inhibitors

Panelists: Bradley J. Monk, MD, FACS, FACOG, University of Arizona, Creighton University, & Arizona Oncology Practice of US Oncology; Ursula Matulonis, MD, Dana-Farber Cancer Institute; David OMalley, MD, The Ohio State University; Matthew Powell, MD, Washington University; Shannon N. Westin, MD, MPH, MD Anderson Cancer Center
Published: Thursday, Apr 26, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s transition now. We’ve talked about surgery. We’ve talked about neoadjuvant therapy. We’ve talked about HIPEC. We’ve talked about all of the chemotherapeutic options. But the field is moving, as Ursula tells us. The field after paclitaxel is poly(ADP-ribose) polymerase (PARP). We live in a PARP world. We’re going to talk about recurrent ovarian cancer in a bit, but is there an opportunity for frontline PARP maintenance in ovarian cancer? Or is it still just useful for second-line therapy?

Ursula Matulonis, MD: Currently, numerous ongoing trials are examining this question.

Bradley J. Monk, MD, FACS, FACOG: Can you tell us about 1 or 2 of them?

Ursula Matulonis, MD: SOLO-1 is a trial where patients with known BRCA mutations, either germline or somatic, are being randomized to olaparib, a tablet formation, versus placebo.

Bradley J. Monk, MD, FACS, FACOG: As frontline maintenance therapy?

Ursula Matulonis, MD: Yes, as frontline maintenance therapy. So, completion of chemotherapy. They enter into clinical remission. We’ll see. Those results are not back yet. And that’s going to bring up another question for our patients, especially as we’re doing more genetic testing when patients are receiving their initial chemotherapy. So, we’re going to have these results by the time that they complete their initial chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: Tell us about PRIMA?

David O’Malley, MD: PRIMA is a trial that looks at niraparib, up front, in all-comers. It was actually originally designed for patients who were HRD–positive, but was amended for all-comers at the time of their approval. So, once again, it only looked at the maintenance setting. Again, a complete or partial response to up-front paclitaxel and carboplatin. If they had a complete or partial response after 6 to 8 cycles, they were then randomized 2:1 to receive niraparib or placebo. The trial was double-blinded, obviously.

Bradley J. Monk, MD, FACS, FACOG: So, SOLO-1—BRCA. Niraparib—PRIMA, looking at all-comers. Both trials looked at these things in the frontline maintenance setting. Why don’t we just give the PARP inhibitor with the chemotherapy?

Shannon N. Westin, MD, MPH: We can, but just not with any PARP inhibitor. With the majority of PARP inhibitors, when we try to combine them with chemotherapy, we can’t. Because of overlapping toxicities, we have to reduce doses too much and we’re getting into ineffective doses of the chemotherapy. However, veliparib is a PARP inhibitor that has been able to sort of play nicely with chemotherapy. You still have to do some dose reduction, but you can give a reasonably biologically active dose in the combination.

There’s a trial called GOG-3005, which has completed enrollment. It basically was able to combine standard chemotherapy with veliparib followed by randomization with the veliparib maintenance. So, you get a question of, does veliparib in addition to chemotherapy help you with induction? Does that get you to your response? Does that get you to your maintenance? And then, does additional veliparib help you push out that progression-free survival and potential overall survival?

Bradley J. Monk, MD, FACS, FACOG: So, SOLO-1—frontline maintenance in BRCA-mutated patients. PRIMA—niraparib in all-comers. GOG-3005—maintenance in all-comers, also giving the PARP inhibitor with the chemotherapy. That’s great.

David O’Malley, MD: How about paclitaxel?

Bradley J. Monk, MD, FACS, FACOG: It’s not going to work. It didn’t work. Let’s emphasize it. The reason maintenance is a good idea is because we have agents that are tolerable. Paclitaxel has cumulative neuropathy, alopecia, fatigue, and bone marrow suppression. It was a good idea when that’s all we had, but it’s not all we have now. Matt, why don’t we just add a PARP inhibitor to bevacizumab?

Matthew Powell, MD: PAOLA-1 is a trial that does that. Patients get bevacizumab maintenance, plus or minus olaparib. This builds on experience from the NCI, with the other VEGF inhibitors coupled with a PARP showing very interesting response rates and survival in both wild-type and BRCA-mutated patients.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s transition now. We’ve talked about surgery. We’ve talked about neoadjuvant therapy. We’ve talked about HIPEC. We’ve talked about all of the chemotherapeutic options. But the field is moving, as Ursula tells us. The field after paclitaxel is poly(ADP-ribose) polymerase (PARP). We live in a PARP world. We’re going to talk about recurrent ovarian cancer in a bit, but is there an opportunity for frontline PARP maintenance in ovarian cancer? Or is it still just useful for second-line therapy?

Ursula Matulonis, MD: Currently, numerous ongoing trials are examining this question.

Bradley J. Monk, MD, FACS, FACOG: Can you tell us about 1 or 2 of them?

Ursula Matulonis, MD: SOLO-1 is a trial where patients with known BRCA mutations, either germline or somatic, are being randomized to olaparib, a tablet formation, versus placebo.

Bradley J. Monk, MD, FACS, FACOG: As frontline maintenance therapy?

Ursula Matulonis, MD: Yes, as frontline maintenance therapy. So, completion of chemotherapy. They enter into clinical remission. We’ll see. Those results are not back yet. And that’s going to bring up another question for our patients, especially as we’re doing more genetic testing when patients are receiving their initial chemotherapy. So, we’re going to have these results by the time that they complete their initial chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: Tell us about PRIMA?

David O’Malley, MD: PRIMA is a trial that looks at niraparib, up front, in all-comers. It was actually originally designed for patients who were HRD–positive, but was amended for all-comers at the time of their approval. So, once again, it only looked at the maintenance setting. Again, a complete or partial response to up-front paclitaxel and carboplatin. If they had a complete or partial response after 6 to 8 cycles, they were then randomized 2:1 to receive niraparib or placebo. The trial was double-blinded, obviously.

Bradley J. Monk, MD, FACS, FACOG: So, SOLO-1—BRCA. Niraparib—PRIMA, looking at all-comers. Both trials looked at these things in the frontline maintenance setting. Why don’t we just give the PARP inhibitor with the chemotherapy?

Shannon N. Westin, MD, MPH: We can, but just not with any PARP inhibitor. With the majority of PARP inhibitors, when we try to combine them with chemotherapy, we can’t. Because of overlapping toxicities, we have to reduce doses too much and we’re getting into ineffective doses of the chemotherapy. However, veliparib is a PARP inhibitor that has been able to sort of play nicely with chemotherapy. You still have to do some dose reduction, but you can give a reasonably biologically active dose in the combination.

There’s a trial called GOG-3005, which has completed enrollment. It basically was able to combine standard chemotherapy with veliparib followed by randomization with the veliparib maintenance. So, you get a question of, does veliparib in addition to chemotherapy help you with induction? Does that get you to your response? Does that get you to your maintenance? And then, does additional veliparib help you push out that progression-free survival and potential overall survival?

Bradley J. Monk, MD, FACS, FACOG: So, SOLO-1—frontline maintenance in BRCA-mutated patients. PRIMA—niraparib in all-comers. GOG-3005—maintenance in all-comers, also giving the PARP inhibitor with the chemotherapy. That’s great.

David O’Malley, MD: How about paclitaxel?

Bradley J. Monk, MD, FACS, FACOG: It’s not going to work. It didn’t work. Let’s emphasize it. The reason maintenance is a good idea is because we have agents that are tolerable. Paclitaxel has cumulative neuropathy, alopecia, fatigue, and bone marrow suppression. It was a good idea when that’s all we had, but it’s not all we have now. Matt, why don’t we just add a PARP inhibitor to bevacizumab?

Matthew Powell, MD: PAOLA-1 is a trial that does that. Patients get bevacizumab maintenance, plus or minus olaparib. This builds on experience from the NCI, with the other VEGF inhibitors coupled with a PARP showing very interesting response rates and survival in both wild-type and BRCA-mutated patients.

Transcript Edited for Clarity 
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Best Practice™: Expert Perspectives to Incorporate Evidence on PARP Inhibitors into Practice and Optimize the Medical Management of Ovarian CancerOct 31, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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