Therapeutic Strategies in Advanced Ovarian Cancer - Episode 9
Bradley J. Monk, MD, FACS, FACOG: Unfortunately, most patients are diagnosed with advanced ovarian cancer. Most of those patients relapse. There’s a significant opportunity in relapse to improve outcomes, and that would be through delaying time to progression; improving quality of life; and, ideally, improving survival. Tom, you participated in a paper that reviewed the new treatment considerations in recurrent ovarian cancer. We used to say it’s platinum resistant, platinum sensitive, it’s over. Tell us about the new multiplex classification of recurrent ovarian cancer.
Thomas Herzog, MD: We’re moving beyond the simple definition of platinum resistant. If you fail platinum on your most antecedent treatment within 6 months, you’re considered to be primarily platinum resistant. If it has been more than 6 months, you’re platinum sensitive. We got a little more sophisticated when we said there was a 6- to 12-month group with intermediate sensitivity. We now realize that it’s about BRCA, other genes, histology, and so much else.
Bradley J. Monk, MD, FACS, FACOG: Number of lines of therapy.
Thomas Herzog, MD: Yes, the number of lines of therapy.
Bradley J. Monk, MD, FACS, FACOG: So, platinum-free interval, molecular signature, histology, and number of lines of therapy at a minimum and, probably, existing toxicities from prior treatments.
Thomas Herzog, MD: You have to take that into account and the underlying comorbidities of the patient, as well.
Bradley J. Monk, MD, FACS, FACOG: Leslie, you told us about frontline bevacizumab. It’s not FDA approved, but it likely will be in June of 2018. We all agreed that there’s going to be some greater uptake, whatever that may be. Bevacizumab is labeled in recurrent disease, as well. Tell us about the current FDA approvals for recurrent disease using bevacizumab.
Leslie M. Randall, MD, MAS: We have 2 approvals, as you know. We use it for platinum-resistant patients in combination with a physician-selected single-agent chemotherapy, such as pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel. We also have an approval in the platinum-sensitive recurrent setting, in addition to carboplatin and Taxol (paclitaxel) as a maintenance strategy.
Bradley J. Monk, MD, FACS, FACOG: So, 5 chemotherapy backbones?
Leslie M. Randall, MD, MAS: Yes.
Bradley J. Monk, MD, FACS, FACOG: Three in resistant disease; 2 in sensitive disease. That’s good.
Leslie M. Randall, MD, MAS: It’s great. I use it all the time.
Bradley J. Monk, MD, FACS, FACOG: Lots of options.
Leslie M. Randall, MD, MAS: Right, and I use these all the time. I think the key to using bevacizumab in the recurrent setting is using it early. As you get into later lines of therapy, it tends to have more toxicity and bowel perforations.
Bradley J. Monk, MD, FACS, FACOG: GOG-0213 led to a label expansion for a platinum-sensitive relapse greater than 6 months—carboplatin, paclitaxel, with or without bevacizumab. When bevacizumab is added to that, there’s a 5-month improvement in overall survival. Integrated into that study was the first overall survival endpoint, which is what matters—study of second irritable debulking. Tom, tell us about the surgical questions regarding GOG-0213, as presented at the 2018 ASCO Annual Meeting.
Thomas Herzog, MD: I think it was a big splash at the meeting. GOG-0213, as you said, had 2 objectives. Again, these were platinum-sensitive patients. The question was, does adding bevacizumab improve overall survival with the adjusted hazard ratio? The answer is yes.
Does secondary cytoreduction improve overall survival? This has been an area in which there has been great controversy over the years. Smaller studies have tried to take this on, as have larger studies, more recently, like the DESKTOP III trial. They presented their progression-free survival data, but their overall survival data are immature. They showed a little over 5-month advantage in progression-free survival, but is that really meaningful when you’re removing the tumor? And so, it makes that a little bit difficult to use as an important endpoint.
Two hundred and forty patients that had surgery and 245 patients with no surgery were randomized. It was an important selection factor, right? You had to decide if the patient was a surgical candidate. That becomes subjective. If the answer was no, they went right to the chemotherapy arm, which was a significant number of the patients. If the answer was yes, then you received randomization as to getting surgery or not getting surgery. The overall survival was 53.6 months in the surgery group and 65.7 months in the no-surgery group.
Bradley J. Monk, MD, FACS, FACOG: Longer if you didn’t have surgery? How is that possible?
Thomas Herzog, MD: That’s correct.
Bradley J. Monk, MD, FACS, FACOG: I told you.
Thomas Herzog, MD: What’s interesting was the R0 rate was 67%, which is pretty close. You can’t argue that the surgery was so inferior to what we found with our European colleagues, because theirs was 72.5%. So, it was pretty close. It was within 5%. It’s very interesting. Your R0 rate was there, but what you gained with R0 was an improved survival if you got to R0. But it didn’t make any difference if you did the surgery or not.
Bradley J. Monk, MD, FACS, FACOG: The R0 patients live longer. Does that mean you should try to operate on them to make them R0?
Leslie M. Randall, MD, MAS: Not if it’s not beneficial.
Bradley J. Monk, MD, FACS, FACOG: That is the stubbornness of gynecologic oncologists.
Leslie M. Randall, MD, MAS: And I’m guilty. I thought this study would be positive. I thought that we would show a benefit.
Bradley J. Monk, MD, FACS, FACOG: It’s a systemic disease. We’ve been talking about chemotherapy here. It’s a systemic disease. I get that they do better if you cut it out, but they don’t do better as if you didn’t operate on them at all.
Transcript Edited for Clarity