Clinical Approach for Platinum-Sensitive Recurrent Ovarian Cancer - Episode 3
Bradley J. Monk, MD, FACOG, FACS:Once a patient responds to frontline treatmentand, generally, that’s a complete response—patients are monitored. They’re monitored for toxicities—generally, that’s neuropathy. Their hair grows back. And they’re also monitored for disease recurrence. And I get it that there’s a lot of controversy about how those patients should be monitored. You’ve basically got 3 options: For symptomatic disease, examine her—and that includes a pelvic exam and talking to her—or you can do radiologic imaging, CT scan, or PET scan; or you can do CA-125. And I think I have a pretty good handle on what we do in the United States. Most people, believe it or not, do CA-125. That doesn’t mean that if the CA-125 goes up, they begin treatment. What it means is that they use the CA-125 maybe every 3 months or so, and if the CA-125 begins to rise, then they do a CT scan or a PET scan, and then they integrate the symptoms that are important, the rate or rise of CA-125 and the radiologic findings, to make a decision. The reason the controversy about CA-125 exists is that people think that when it goes up, you have to treat. No. We use the CA-125 as a trigger, as a triage to order imaging. It’s OK and certainly acceptable if you don’t want to do imaging ever and you don’t want to do CA-125 and focus on symptoms. But, in today’s world, where we have many therapies for that patient who develops a recurrence, many individuals and patients want to know early if their cancer is recurring. And, in this particular patient, CA-125 is a marker and it can be monitored.
This particular patient recurred more than 2 years after initial treatment, which is a little longer than what you would expect. Why? Because she had aBRCAmutation.BRCAmutations have a longer time to progression. So, for this particular patient, more than 2 years of time to recurrence is pretty common. And so, she would then be evaluated, sometimes considered for secondary debulking surgery. Again, that’s not evidence-based, but I get it, given the long treatment-free interval, if there was an isolated recurrence, maybe some would say she should have another operation; most wouldn’t. And particularly if you monitor her closely, the amount of disease she would have when she recurs is small. So, she would be evaluated for treatment, and this would be called a platinum-sensitive relapse. It recurred more than 6 months later, and that would be our threshold.
So, when we see a patient with ovarian cancer, we look at 4 things: the cell typethis is a high-grade serous tumor; the platinum-free interval is more than 2 years; the molecular signature,BRCAshe has a germlineBRCAmutation; and the number of lines of therapy. And if you wanted to add a fifth thing, it would be existing toxicities. So, she would be evaluated for retreatment, and she would be treated with a platinum doublet, generally 3 choices: carboplatin/paclitaxel again, carboplatin/gemcitabine, or carboplatin/pegylated liposomal doxorubicin (PLD), but platinum doublet. Carboplatin always and either paclitaxel, gemcitabine, or PLD. So, you’d have to make that decision, and then you would have to make the decision whether or not she should have bevacizumab. In December of 2016, bevacizumab was FDA approved for treating platinum-sensitive relapse, just like this patient had. It’s obviously acceptable to do various things, but most would treat this patient now in the setting of platinum-sensitive relapse with carboplatin, a second medication, and bevacizumab.
And there are actually 2 chemotherapy backbones that are FDA approved in platinum-sensitive relapse: carboplatin/gemcitabine/bevacizumab, which had a progression-free survival advantage of around 4 months, or carboplatin/paclitaxel again with bevacizumab, which has a 5-month improvement in overall survival based on GOG 213. I invite you to read that; Robert Coleman published it inLancet Oncologyin 2017. And so, that’s what this patient hadcarboplatin/paclitaxel because she could have paclitaxel again and she didn’t have existing neuropathy. The treating physician was persuaded by the survival advantage of 5 months with carboplatin/paclitaxel/bevacizumab and bevacizumab in maintenance. Now, the median and the treatment until progression in the frontline setting is 15 months, but in platinum-sensitive relapse, when used, it’s until progression. And the median time to progression is 14 months, and indeed she did just over that.
Transcript edited for clarity.
Platinum-Sensitive Recurrent Ovarian Cancer