Advanced Ovarian Cancer: New Perspectives on Systemic Therapy - Episode 1
Bradley J. Monk, MD, FACS, FACOG: This has been another transformative year in gynecologic cancer. As practice-changing data continue to emerge in this OncLive Peer Exchange® discussion, my colleagues and I will discuss recent data, including that from the European Society for Medical Oncology Congress 2019 meeting in Barcelona, Spain. We’ll provide perspective on how the latest research will translate to your practice and hopefully improve patient outcomes. My name is Brad Monk. I’m a gynecologic oncologist from Phoenix, Arizona, a professor of gynecologic oncology at the University of Arizona and Creighton University, and also part of the US Oncology Network.
Joining me today on this distinguished panel are:
Dr Kathleen Moore, the Virginia Kerley Cade Chair in Developmental Therapeutics, an associate director of clinical research, and the director of the Oklahoma TSET Phase I Program at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma. That’s a mouthful. Katie, thank you for joining us. I know you’re busy, and it’s really my pleasure to have you with us.
Kathleen Moore, MD: Thanks.
Bradley J. Monk, MD, FACS, FACOG: Dr Robert Coleman, a professor in the department of gynecologic oncology and reproductive medicine, the executive director of the Cancer Network Research, and the Ann Rife Cox Chair in Gynecology at The University of Texas MD Anderson Cancer Center in Houston, Texas.
You guys need shorter titles. Why can’t I just say, “my good friend Katie Moore from Oklahoma, and Rob Coleman from MD Anderson?”
Dr Shannon Westin, an associate professor and the director of early drug development in the department of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Center in Houston, Texas. Shannon, thank you.
Shannon N. Westin, MD, MPH: Thank you for having me.
Bradley J. Monk, MD, FACS, FACOG: Last, but not least, Dr Michael J. Birrer, a professor of medicine, hematology, and oncology and the Evalina B. Spencer Chair in Oncology at the University of Alabama at Birmingham in Birmingham, Alabama.
Michael J. Birrer, MD, PhD: Thanks, Brad.
Bradley J. Monk, MD, FACS, FACOG: You’re welcome, and thank you. Thank you for joining me. Let’s begin. We’re going to have a robust conversation about ovarian cancer. I’d like to start at the beginning, which is always a good thing. Shannon, most patients with epithelial ovarian cancer are diagnosed with advanced stages. Most patients are high-grade serous.
Shannon N. Westin, MD, MPH: Correct.
Bradley J. Monk, MD, FACS, FACOG: What is the standard treatment? I think it’s a global standard for treating newly diagnosed advanced high-grade serous ovarian tubal or peritoneal cancer.
Shannon N. Westin, MD, MPH: Yes. Our standard treatment is going to be a combination of surgery and chemotherapy—sometimes surgery first, sometimes chemotherapy first. Our goal from surgery, wherever it happens in the continuum, is to get down to no gross residual disease. From a chemotherapy standard, we’re generally going to use paclitaxel and carboplatin intravenously. We can also use it intraperitoneally, and I think we’re going to get into some of the other combinations that we can see going toward that.
Bradley J. Monk, MD, FACS, FACOG: We’ve talked about intraperitoneal administration and how it’s been falling out of favor. What sort of carboplatin and paclitaxel doses?
Shannon N. Westin, MD, MPH: Typically, what I use is intravenous every 3 weeks, and I give 175 mg/m2 of paclitaxel and carboplatin at an area under the curve of 6.
Bradley J. Monk, MD, FACS, FACOG: Katie, obviously there’s been this emerging information about bevacizumab. Bevacizumab was FDA approved on June 12, 2018. Tell us about the opportunity of bevacizumab in frontline treatment with chemotherapy and in maintenance.
Kathleen Moore, MD: There are 2 big frontline studies that demonstrated efficacy for bevacizumab with chemotherapy and afterward as maintenance for a variable amount of time—for about a year. In both of those studies, it has very consistently demonstrated as statistically significant and clinically meaningful improvement in progression-free survival—that means the time that a patient has from the end of chemotherapy until she recurs.
That’s meaningful to patients. Bevacizumab is well tolerated. There are certain subgroups that may benefit a bit more than others, which is speculative, but all patients seem to benefit somewhat, and it’s become the standard of care in several lines of chemotherapy for our patients. It’s a very important asset.
Bradley J. Monk, MD, FACS, FACOG: Michael, she mentioned there are some patients who benefit, perhaps based on either molecular or clinical biomarkers. Who’s the best candidate for frontline bevacizumab?
Michael J. Birrer, MD, PhD: That’s a great question, and we certainly have biomarkers that have been developed. I like to claim CD31 as an interesting one. IL-6 is in the play, too, but none of them has been validated. Unfortunately, they can’t be used to predict who would benefit most. I think most of us use clinical criteria. We have a patient who has a lot of ascites—who maybe has large disease or is part of that high-risk group that ICON7 talked about. They might be a patient who would benefit more from this drug. With what we’re going to talk about later regarding the PARP inhibitors, that may evolve a little bit.
Bradley J. Monk, MD, FACS, FACOG: Volume of disease is perhaps 1 of the most important factors. Rob, you’ve been very interested in this approval process. GOG-0218 was published in 2011, but it took 7 years to get FDA approval. Why the delay? Why did it take 7 years after the European approval to come to the United States?
Robert L. Coleman, MD, FACOG, FACS: It’s a good question. I don’t think it was the basis from an advocacy standpoint, right? I think we were all really convinced of that. It was a strategic move. It was the right time, and there had been multiple other approvals. The databases have been cleaned. It was the right time. We felt it probably should have been sooner.
Bradley J. Monk, MD, FACS, FACOG: Right.
Robert L. Coleman, MD, FACOG, FACS: There were a number of factors, which were not necessarily all related to science. Those were things we had to deal with.
Bradley J. Monk, MD, FACS, FACOG: One of the things I’ve heard you say before is that several years ago, there was an opportunity to perhaps improve overall survival. It took an evolution of the thought process that progression-free survival was a more reliable and relevant endpoint because of the long postprogression survival. You agree with that, right?
Robert L. Coleman, MD, FACOG, FACS: Yes, and it’s a key point because it really impacts the way that we design trials. If you really want to address an OS [overall survival] endpoint, you have to overpower it for the more immediate endpoints. You and I have talked about this many times. You run the risk of having a significant but not clinically meaningful endpoint as you overpower for an endpoint that may take 3 years to achieve. The overall survival endpoint had obviously been linked to approval in the past, so now I think we’ve been convincing in showing that these earlier endpoints are more informative and that later endpoints can be confounded by subsequent drugs.
Michael J. Birrer, MD, PhD: The irony here was that the EMA [European Medicines Agency] approval used the 2018 data.
Bradley J. Monk, MD, FACS, FACOG: Right? There are 2 studies. One is the European ICON7, and the other is the American GOG-0218. The Europeans used the American study. I think it’s because the American study was placebo controlled and had all the bells and whistles. I’ve already said that it takes 2 studies to convince anyone of anything. Those 2 studies were complementary.
Transcript Edited for Clarity