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Ongoing Research in Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACOG, FACS, University of Arizona; Creighton University School of Medicine; Arizona Oncology; Kathleen N. Moore, MD, University of Oklahoma; Elena S. Ratner, MD, Yale University School of Medicine; Brian M. Slomovitz, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System
Published: Tuesday, Jun 25, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So you have IMagyn050—bevacizumab/atezolizumab. And then you’ve got olaparib with durvalumab, and olaparib with pembrolizumab. And then you have FIRST, which is niraparib/dostarlimab. And then ATHENA, which is, “We’re just going to do it in maintenance.”

So that’s 5 trials, frontline, and now I’m here to tell you there’s a sixth and a seventh. That’s just with PARP [poly ADP ribose polymerase]. PARP can either be done alone, all-comers, called PRIMA—niraparib. So your study SOLO-1 was only BRCA patients.

Kathleen N. Moore, MD: Correct.

Bradley J. Monk, MD, FACOG, FACS: And we want to do more than BRCA. Tell us about PRIMA now.

Kathleen N. Moore, MD: So PRIMA is very similar to SOLO-1. It is similar but different. It took a different population of patients. As I mentioned earlier, SOLO-1 were great prognosis patients. PRIMA actually took high-risk sorts of frontline patients with lots of disease—residual disease, post cytoreduction—so a more high-risk of the high-risk advanced stage who did have complete or partial responses to their frontline chemotherapy, and then randomized them to maintenance niraparib or placebo.

The other difference is that it’s stratified by HRD [homologous recombination deficiency] status. So not by BRCA, but HRD. Of course, the BRCA patients will be stratified appropriately, but you are also  stratifying based on at least the Myriad assay for loss of homologous recombination.

Bradley J. Monk, MD, FACOG, FACS: And we want that. We like SOLO-1, but it’s just BRCA, 25%. If we could do BRCA-like, as you said, HRD, if you will, then maybe it would be at least half of the patients.

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And who knows. We’ve never even studied all-comers because in the second-line it’s all-comers.

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And then finally, adding PARP to chemotherapy. Does that make any sense—GOG-3005 with veliparib?  

Brian M. Slomovitz, MD: We’re waiting to receive the results of GOG-3005 with veliparib. It would be the fourth PARP inhibitor. The study has been closed and we’ll have to see. We’re not sure.

Bradley J. Monk, MD, FACOG, FACS: It’s rapidly evolving, so fast it makes your head spin. Back to our NCCN [National Comprehensive Cancer Network] guideline expert, the No. 1 recommended NCCN treatment is a clinical trial.

Elena S. Ratner, MD: Correct, always.

Bradley J. Monk, MD, FACOG, FACS: You were talking to me about that prior. I think all of us are committed to clinical trials. Clinical trials are the best opportunity for discovery. I’m here to tell you that in virtually every clinical trial that we’ve ever done in ovarian cancer, the experimental arm has never been worse. It’s not always better, but virtually, it’s never worse. There are some isolated exceptions. You said avelumab versus pegylated liposomal doxorubicin; platinum-resistant, avelumab wasn’t quite as good as pegylated liposomal doxorubicin. But I would argue both of them were bad. So when you talk about adding these targeted therapies, it really appears that that’s the best opportunity for your patients.

So I want to close with the fourth targeted therapy. We talked about antiangiogenic/PARP inhibitors in immuno-oncology and combinations. The next is antibody drug conjugates. Antibody drug conjugates, T-DM1 in breast cancer, HER2/neu, and a cytotoxic payload. We have been so excited about this mirvetuximab soravtansine, which is an antibody drug conjugate to the folate receptor called FORWARD I. We happen to have the principal investigator, and I know you know a lot about that study. It’s not in the public domain, but there is some stuff in the public domain. Tell me about the design of FORWARD I and what’s in the public domain?

Kathleen N. Moore, MD: FORWARD I is a randomized study for patients with recurrent disease, 1 to 3 prior lines of therapy, and tumor that either is medium or high to expressors of folate receptor alpha, as defined by immunohistochemistry and by a standardized test. And it randomized patients to either physician’s choice of chemotherapy, which was topotecan, paclitaxel, or pegylated liposomal doxorubicin, or single-agent mirvetuximab, with a progression-free survival endpoint.

Bradley J. Monk, MD, FACOG, FACS: Antibody drug conjugate versus physician’s choice chemotherapy. I love it. And in the phase I trial, the response rate was?

Kathleen N. Moore, MD: Forty-seven percent.

Bradley J. Monk, MD, FACOG, FACS: Forty-seven percent. Let’s get it done. And…?

Kathleen N. Moore, MD: And unfortunately, the primary endpoint was negative.

Bradley J. Monk, MD, FACOG, FACS: Yes, so stay tuned.

Kathleen N. Moore, MD: Yeah, we’re working on it.

Bradley J. Monk, MD, FACOG, FACS: We’re working on it. And again, it’s a superiority endpoint. Just because it doesn’t beat something doesn’t mean that it’s not active, and I think that’s the lesson. I also am here to tell you that many of our studies are randomized to 2 drugs versus 1. Or 3 drugs versus 2. Or in the PARP inhibitor space, versus observation. So it’s very difficult to do 1-to-1, OK?

Kathleen N. Moore, MD: Right.

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So you have IMagyn050—bevacizumab/atezolizumab. And then you’ve got olaparib with durvalumab, and olaparib with pembrolizumab. And then you have FIRST, which is niraparib/dostarlimab. And then ATHENA, which is, “We’re just going to do it in maintenance.”

So that’s 5 trials, frontline, and now I’m here to tell you there’s a sixth and a seventh. That’s just with PARP [poly ADP ribose polymerase]. PARP can either be done alone, all-comers, called PRIMA—niraparib. So your study SOLO-1 was only BRCA patients.

Kathleen N. Moore, MD: Correct.

Bradley J. Monk, MD, FACOG, FACS: And we want to do more than BRCA. Tell us about PRIMA now.

Kathleen N. Moore, MD: So PRIMA is very similar to SOLO-1. It is similar but different. It took a different population of patients. As I mentioned earlier, SOLO-1 were great prognosis patients. PRIMA actually took high-risk sorts of frontline patients with lots of disease—residual disease, post cytoreduction—so a more high-risk of the high-risk advanced stage who did have complete or partial responses to their frontline chemotherapy, and then randomized them to maintenance niraparib or placebo.

The other difference is that it’s stratified by HRD [homologous recombination deficiency] status. So not by BRCA, but HRD. Of course, the BRCA patients will be stratified appropriately, but you are also  stratifying based on at least the Myriad assay for loss of homologous recombination.

Bradley J. Monk, MD, FACOG, FACS: And we want that. We like SOLO-1, but it’s just BRCA, 25%. If we could do BRCA-like, as you said, HRD, if you will, then maybe it would be at least half of the patients.

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And who knows. We’ve never even studied all-comers because in the second-line it’s all-comers.

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And then finally, adding PARP to chemotherapy. Does that make any sense—GOG-3005 with veliparib?  

Brian M. Slomovitz, MD: We’re waiting to receive the results of GOG-3005 with veliparib. It would be the fourth PARP inhibitor. The study has been closed and we’ll have to see. We’re not sure.

Bradley J. Monk, MD, FACOG, FACS: It’s rapidly evolving, so fast it makes your head spin. Back to our NCCN [National Comprehensive Cancer Network] guideline expert, the No. 1 recommended NCCN treatment is a clinical trial.

Elena S. Ratner, MD: Correct, always.

Bradley J. Monk, MD, FACOG, FACS: You were talking to me about that prior. I think all of us are committed to clinical trials. Clinical trials are the best opportunity for discovery. I’m here to tell you that in virtually every clinical trial that we’ve ever done in ovarian cancer, the experimental arm has never been worse. It’s not always better, but virtually, it’s never worse. There are some isolated exceptions. You said avelumab versus pegylated liposomal doxorubicin; platinum-resistant, avelumab wasn’t quite as good as pegylated liposomal doxorubicin. But I would argue both of them were bad. So when you talk about adding these targeted therapies, it really appears that that’s the best opportunity for your patients.

So I want to close with the fourth targeted therapy. We talked about antiangiogenic/PARP inhibitors in immuno-oncology and combinations. The next is antibody drug conjugates. Antibody drug conjugates, T-DM1 in breast cancer, HER2/neu, and a cytotoxic payload. We have been so excited about this mirvetuximab soravtansine, which is an antibody drug conjugate to the folate receptor called FORWARD I. We happen to have the principal investigator, and I know you know a lot about that study. It’s not in the public domain, but there is some stuff in the public domain. Tell me about the design of FORWARD I and what’s in the public domain?

Kathleen N. Moore, MD: FORWARD I is a randomized study for patients with recurrent disease, 1 to 3 prior lines of therapy, and tumor that either is medium or high to expressors of folate receptor alpha, as defined by immunohistochemistry and by a standardized test. And it randomized patients to either physician’s choice of chemotherapy, which was topotecan, paclitaxel, or pegylated liposomal doxorubicin, or single-agent mirvetuximab, with a progression-free survival endpoint.

Bradley J. Monk, MD, FACOG, FACS: Antibody drug conjugate versus physician’s choice chemotherapy. I love it. And in the phase I trial, the response rate was?

Kathleen N. Moore, MD: Forty-seven percent.

Bradley J. Monk, MD, FACOG, FACS: Forty-seven percent. Let’s get it done. And…?

Kathleen N. Moore, MD: And unfortunately, the primary endpoint was negative.

Bradley J. Monk, MD, FACOG, FACS: Yes, so stay tuned.

Kathleen N. Moore, MD: Yeah, we’re working on it.

Bradley J. Monk, MD, FACOG, FACS: We’re working on it. And again, it’s a superiority endpoint. Just because it doesn’t beat something doesn’t mean that it’s not active, and I think that’s the lesson. I also am here to tell you that many of our studies are randomized to 2 drugs versus 1. Or 3 drugs versus 2. Or in the PARP inhibitor space, versus observation. So it’s very difficult to do 1-to-1, OK?

Kathleen N. Moore, MD: Right.

Transcript Edited for Clarity
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