Recurrent Advanced Ovarian Cancer: Case Impressions

Kathleen Moore, MD:Today we’re going to discuss a very typical case of advanced ovarian cancer. This is a woman who initially presented with advanced stage disease. She was assessed by a gynecologic oncologic surgeon and was deemed appropriate for surgery. She had an attempt at cytoreductive surgery, which was unfortunately not successful, and she ended up with residual disease. She then went on to receive what would be considered the standard of care, which is combination chemotherapy with carboplatin and paclitaxel. She had a complete response to that and enjoyed a fairly long remission—for about 2 years—which is really kind of the average for when we see our patients start to recur. So this isn’t surprising.

At the 2-year point, she was reassessed and felt to be appropriate for retreatment with platinum-based chemotherapy. And so, again she was treated with carboplatin and paclitaxel, but this time the targeted therapy bevacizumab was added to chemotherapy to maximize her response to chemotherapy. She again had a complete clinical response after 6 cycles, and then was placed on maintenance therapy with bevacizumab given every 3 weeks until the time of progression. Again, she enjoyed a fairly long platinum-free interval—of about 1.5 years—at which point she progressed again, or recurred again. So again, she was assessed by her treating team. She was found to be appropriate for retreatment with platinum-based chemotherapy. She had paclitaxel twice before, so the other partners for carboplatin that we can consider are gemcitabine or pegylated liposomal doxorubicin.

Gemcitabine was selected in this case, and she received carboplatin and gemcitabine again. This is her third platinum-based regimen. After 6 cycles, she was again in a complete clinical response. And so, no maintenance was used in this setting of therapy. She went on for about 10 to 11 months before she re-presented with an elevated CA 125 [cancer antigen 125] and what we would term as measurable disease, or disease that could be measured reproducibly on her imaging. And so, she has recurred again and now is presenting for consideration of treatment.

I think this case is, again, very standard, unfortunately, for our patients with advanced ovarian cancer, despite the disease being exquisitely chemotherapy-sensitive in the first-line, and we’ve seen this multiple times in this patient. It’s very rarely cured with surgery and frontline chemotherapy. Long-term disease-free survival remains dismally low, in about 10% to 12% of patients, so recurrences are expected. When patients recur, we consider a number of things, in terms of how we’re going to treat them, probably the most important being the response to prior platinum-based chemotherapy, and the duration of time since that, what we call the penultimate platinum-based chemotherapy.

But another thing we consider is the patient’s cell type of her ovarian cancer. Is this a high-grade serous as it is in this case? Or does she have a clear cell cancer or mucinous cancer? Those may play into decision making for novel therapeutics, in particular. We pay attention to residual toxicity from her last chemotherapy, and this patient had paclitaxel twice. And so, consideration of neuropathy would be very high for subsequent lines of chemotherapy, and also the patient’s willingness to have her hair fall out again. That is another thing that we have to think about.

In some settings, we may think about whether the patient should undergo a secondary cytoreduction surgery. There has been a very large clinical trial done in the United States that would argue that is not a good idea and that patients who undergo the surgery actually do not live as long. And so that has fallen out of favor in some schools. However, there’s another trial ongoing in Europe that is asking the same questions. So many are still considering this as an option for patients. And so, this is probably something that should be on the table, especially for patients potentially with oligometastases. Although I again will say there was a randomized phase 3 study that found absolutely no benefit for secondary cytoreduction, even in patients with oligometastases. So I think people are thinking about it, but the evidence would not support it any longer.

And also, shared decision making with the patient about what her goals are. Also, to plan the therapies that are selected. You can see this in play with each line of chemotherapy for her. Now she’s presented again with what we would deem a recurrence that would still be appropriate for retreatment with platinum potentially. But there are other options as well that this patient can consider, and other testing that hasn’t been done in her case yet that we need to discuss that may influence the type of therapy that’s offered.

Transcript edited for clarity.

Case: A 58-Year-Old Female With Heavily Pretreated Recurrent Ovarian Cancer

H & P

• 58-year-old female diagnosed in 2014 with stage IV ovarian cancer
  • Pathology: high-grade serous carcinoma, epithelial ovarian cancer
  • CA-125: 460 U/mL
  • CT with contrast of the pelvis, abdomen, and chest revealed a 4-cm mass in the left ovary and peritoneal carcinomatosis
  • Patient underwent suboptimal debulking surgery; residual disease 1.5 cm
  • Received IV/IP carboplatin/paclitaxel (6 cycles); achieved complete remission
• 2 years later (2016) symptoms returned; CA 125, 255 U/mL; ECOG: 1
  • Received carboplatin/paclitaxel (6 cycles) and bevacizumab; achieved good partial remission; CA 125, 45 U/mL; continued on bevacizumab maintenance
• 1.5-years following second-line therapy (2017), again presented with symptoms; CA 125, 550 U/mL; ECOG: 0
  • Genetic testing;gBRCA1/2wild-type
  • Received carboplatin/gemcitabine (6 cycles); CA 125, 46 U/mL; achieved complete remission
• Currently:
  • CA 125, 620 U/mL
  • CT shows several small masses in the lung left lower lobe (largest is 3 cm)
  • ECOG: 0