Ovarian Cancer: Therapeutic Management at Recurrence

Thomas Herzog, MD:At recurrent disease, again, the first thing you need to do is decide whether you want to do surgery or not, being that she’s platinum-sensitive. And the second thing is, what are you going to use in terms of your systemic treatment? So, certainly, platinum-based therapy—again, with data showing pegylated liposomal doxorubicin, paclitaxel, and gemcitabine—would be perfect partners. And then, there’s the decision to add bevacizumab or not. You have to put that into the context of the recent PARP approvals for platinum-sensitive disease as well and figure out how you’re going to sequence these drugs, if she’s indeed a candidate for a PARP inhibitor.

Patients who have peritoneal implants tend not to do as well, especially those that are generating ascites. So, that’s one of the things that would be troublesome in terms of prognosis for this patient. You would much rather see an isolated mass, one that’s amenable to surgical resection. Patients with small miliary disease or carcinomatosis tend not to do as well in terms of prognosis. A patient who develops peritoneal metastases often has signs and symptoms of ascites. And that was the case with this particular patient, which makes me very interested in administering bevacizumab, which does a wonderful job in terms of responses that we see with ascites. And so, I tend to make sure that bevacizumab is part of the regimen when someone presents with this pattern.

So, I’ve had a fair amount of experience of using bevacizumab with both of the backbones that were in the phase III trials—GOG-213 with paclitaxel and carboplatin, as well as with the OCEAN’s trial. I think that the tolerabilities have been good with both of those backbones. You sometimes need to make adjustments for the patient. If you have a patient, for example, who has had a significant amount of neuropathy, that would be someone whom I would tend to treat with the OCEAN’s regimen. If it has been a shorter interval and they’ve just received carboplatin/paclitaxel—perhaps you’re in that 6- to 9-month window, for example—it may make it more appealing to try a different agent that the tumor has not been exposed to. Those are some of the nuances that I think about when I’m trying to make a decision between those particular compounds.

A patient who recurs in less than 6 months would be characterized as platinum-resistant. Generally, what we do in those cases is we have a choice of multiple agents, and again, a decision is made whether to pair that with bevacizumab or not. So, there’s a number of things that go into that thought process: how symptomatic the patient is, what exactly are we trying to accomplish with therapy in terms of are we eliminating symptoms, are we treating an elevated CA-125, are we perhaps trying to relieve a bowel obstruction? All those types of things can change the choices of therapy. In general, what we do is we look at taking agents that are nonplatinum and exposing the patient to those in some type of sequence that makes sense. There are a lot of things that we need to consider in terms of where does the patient live, what kind of schedule is going to make sense in terms of logistics? Is she currently working? What kind of side effects has she had from primary treatment? So, lots of different variables that need to be accounted for in trying to make a decision of how to treat a platinum-resistant patient.

One important thing to remember when you’re treating a patient with bevacizumab is that you need to pay attention to the patient’s blood pressure. So, frequent monitoring is indicated. We tend to make sure that the patient’s blood pressure stays under control. That allows us to hopefully avoid having to either do dose reductions or dose delays with the bevacizumab. There are various agents and classes of agents that can be added to control the blood pressure, but it all starts with careful monitoring throughout administration of bevacizumab.

Transcript edited for clarity.

May 2015

• A 56-year-old woman presented to her gynecologist with urinary frequency and persistent abdominal bloating. The patient reports maintaining normal activities and a moderate exercise.
  • PMH: Hypertension, well-controlled or spironolactone
  • Abdominal ultrasound showed a complex mass in the right pelvis measuring 4.5 X 5.0 X 7.5 cm
  • Physical exam: fluid wave test positive for ascites
  • CA-125, 622 U/ml
• She was referred to a gynecologic oncologist for further evaluation.
• CT of the pelvis and abdomen showed a right complex pelvic mass, ascites, and omental cake. No other peritoneal lesions were visualized.
• Based on CT findings, she was scheduled for surgery.
• The patient underwent complete resection with no residual disease remaining.
• Diagnosis, epithelial ovarian cancer, stage IIIC
• She received 6 cycles of carboplatin every 3 weeks (AUC 6) and weekly paclitaxel (80 mg/m²) for 18 weeks.
• Follow up labs showed normalization of CA-125 to less than 10 U/ml

April 2017

• Almost 2 years later, the patient reported having symptoms of persistent abdominal distention and weight loss. She reports feeling tired and napping during the day.
  • CA-125 level, 330 U/ml
  • CT scan showed peritoneal seeding consistent with carcinomatosis
• Diagnosis: platinum-sensitive recurrent ovarian cancer
• The patient was started on bevacizumab (15 mg/kg) plus 6 cycles of carboplatin (AUC 5) and paclitaxel (175 mg/m²) every 3 weeks with a plan for bevacizumab maintenance therapy.
• After 2 cycles of therapy, she developed grade 2 hypertension (156/94 mm Hg); this was subsequently controlled by adding an ACE inhibitor to her diuretic.
• The patient has continued therapy without incident.