Ovarian Cancer: Looking Toward Later-Line Therapy

David O’Malley, MD:The sequencing of recurrent ovarian cancer really comes into play with what the patient has had previously. If this patient had not elected to go on to a PARP inhibitor and she was found to have a molecular change in aBRCAmutation or germlineBRCAmutation, I clearly would want to get them a PARP inhibitor.

The options for recurrent ovarian cancer are all over the board. They include cytotoxic therapies, as well as other biologics, like utilizing bevacizumab. The options as we move forward would be dose-dense paclitaxel, every 3-week paclitaxel, Gemzar (gemcitabine) single-agent therapy with a platinum, or paclitaxel also to be used with a platinum. We also would look at pegylated liposomal doxorubicin. Topotecan has indication, and there are other agents that are listed within the guidelines that we would consider. But those 3 or 4 would be the most commonly used. Clearly, a clinical trial in this patient population would be my first choice, as we have so many exciting agents that are being developed right now and being combined, which would probably give patients a better chance of responding than what’s currently clinically available.

The rapidly changing landscape of epithelial ovarian cancer, which also includes fallopian tube and primary peritoneal cancer, is awesome. We now have options available to our patients that we didn’t even dream of just a few years ago. We have gone through a long period with no new drugs. Now we have 4 new biologics available to our patients: bevacizumab, rucaparib, niraparib, and olaparib. Those options, and trying to keep up on the differences between them, are so important. We need to make sure we’re doing the best for our patients, because each one of these has its own unique side effect profile, as well as dosing schedule.

Transcript edited for clarity.

Case: A 69-year-old Woman with Advanced Serous Ovarian Cancer

January 2017

• A 69-year-old Caucasian woman presented to the emergency department with shortness of breath
• PMH: mild HTN and DM, medically managed; morbid obesity
• PE: large volume ascites
• CT angiography (chest) showed large bilateral pulmonary effusions, no pulmonary thromboembolism
• Laboratory findings remarkable for CA 125, 525U/mL
• Thoracentesis (1500 cc); cytology showed high grade adenocarcinoma
• Paracentesis (4500 cc); cytology showed high grade adenocarcinoma
• Core biopsy of omentum; high grade serous carcinoma; p53 (+)/ PAX 8 (+) /WTI and CX 7 (+); BRCA1/2 wild-type
• The patient underwent debulking surgery with incomplete cytoreduction
• She was treated as part of a clinical trial with carboplatin/paclitaxel + bevacizumab followed by continuous bevacizumab maintenance

April 2018

• Fifteen months later, the patients complained of severe abdominal bloating and fatigue
• Imaging showed multifocal recurrence within the abdominal cavity
  • CA 125, 322 U/mL
  • ECOG 1
• She was started on carboplatin/docetaxel
• After 6 cycles of therapy she had a partial response to therapy with bulky residual disease
• She was initiated on rucaparib maintenance therapy, 600 mg BID
• Hb fell to 7.2 g/dl, managed with treatment interruption and then dose reduction to rucaparib 500 mg