Clinical Approach for Platinum-Sensitive Recurrent Ovarian Cancer - Episode 3

Monitoring and Managing Patients With Ovarian Cancer

February 28, 2018

Bradley J. Monk, MD, FACOG, FACS:Once a patient responds to frontline treatment—and, 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 type—this is a high-grade serous tumor; the platinum-free interval is more than 2 years; the molecular signature,BRCA—she 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 had—carboplatin/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

September 2014

  • A 40-year old Caucasian female presented to her gynecologist with abdominal pain and increased urinary urgency and frequency
    • PMH: unremarkable
    • FH: mother died of breast cancer at age 46
    • PE: tenderness in abdominal right lower quadrant; shifting dullness on abdominal palpation and percussion
    • Ultrasound: Abdominal and pelvic ultrasound showed a right-sided solid pelvic mass and ascites
  • The patient was then referred to a gynecologic oncologist
    • Genetic testing was positive for BRCA1 mutation
    • Abdominal/pelvic CT findings showed a 5-cm x 2.5 cm x 3-cm right pelvic mass; ascites and omental cake was noted
    • CA125, 998 U/mL
  • Biopsy findings showed stage 3C epithelial ovarian cancer
  • Hysterectomy, bilateral salpingo-oophorectomy, and omentectomy was performed and optimal debulking was achieved (residual disease <1 cm)
  • Treatment was initiated with IV/IP carboplatin/paclitaxel
    • After 6 cycles of therapy, CA-125 level declined to 9.3 U/ml.
    • Chemotherapy was tolerated well and without any unexpected toxicities

November 2016

  • The patient reported feeling bloated and exhausted
  • CT scan confirmed disease recurrence with ascites
  • She was treated with carboplatin/paclitaxel/bevacizumab for 6 cycles and had a good response to therapy
  • Following completion, she was continued on maintenance bevacizumab
  • She continued to show improved response

January 2018

  • The patient reported back with complaints of weight loss and abdominal distension
  • CT scan revealed presence of small diffuse intraperitoneal masses