Optimizing Therapy in Recurrent Ovarian Cancer

David O’Malley, MD:Fifteen months after completing her platinum doublet, unfortunately, this patient presented with an increase in abdominal discomfort and distension. She was found to have multifocal recurrence at that time, with a significantly elevated CA 125. Her test at the time of primary diagnosis showed that she wasBRCAwild-type and that she had no significant abnormalities in her tumor. Unfortunately, she presented approximately 15 months after completing her platinum doublet with an increase in abdominal discomfort, as well as early satiety and bloating.

A CAT scan at that time showed a multifocal disease within the abdominal cavity. Her CA 125 was significantly elevated. After a discussion of the options of treatment, she elected for carboplatin and docetaxel. She had a partial response and did have persistent disease, which is defined as greater than 2 cm, but her CA 125 had almost normalized. At that time, we discussed with her the options of therapy. She elected to proceed with rucaparib maintenance therapy. During that time, she experienced the toxicity of anemia down to about 7 g/dL. We managed that by interrupting the dose and then dose reducing from 600 mg down to 500 mg.

When we discussed the options of treatment for her recurrence, we looked at individualizing care for this patient. There are multiple options of treatment. The first thing we discussed is, should we proceed with a surgical excision of her recurrent disease? The recent DESKTOP study that has been reported showed a progression-free survival improvement, but overall survival has not been reported. GOG-213, which Dr. Robert Coleman is the PI on, we expect to report out at ASH with regard to the surgical question.

As we look at these options, we look to see where her disease is. We’re more apt to consider surgery the longer out she is from completing her chemotherapy and the more focal the disease is. In this patient, where she’s approximately out a year and a half and she had multifocal disease—and because of her other comorbidities, which we really want to discuss—the decision was made that we thought this surgery would not benefit her. We proceeded directly to chemotherapy, somewhat because she was quite symptomatic also.

The options are really platinum doublets, and you can utilize pegylated liposomal doxorubicin with carboplatin versus Gemzar (gemcitabine), as in the OCEANS protocol, as well as platinum and paclitaxel. This patient had preexisting neuropathy from her initial paclitaxel, so she elected for docetaxel. The other options are for maintenance therapy. With regard to maintenance therapy, we have observation, thus meaning no therapy. Because she did have a partial response and persistent disease, it would be very reasonable to continue her chemotherapy. Also, bevacizumab is approved for platinum-sensitive maintenance therapy plus treatment. She had already had bevacizumab, so for that reason, we did not proceed with it at this time.

The other options are PARP inhibitors. PARP inhibitors are indicated as maintenance in platinum-sensitive disease. Now, when we look at the options for platinum-sensitive maintenance and we’ve taken bevacizumab off the table because of her previous exposure, we are then deciding between the 3 agents that are available.

You really need to look at the individual patients to make this decision. The best data on bulky disease, which we refer to as disease greater than 2 cm, is from the ARIEL3 protocol. Those patients were allowed to go on to trial even though they had disease greater than 2 cm on a CAT scan, but they did have to normalize their CA 125. When we look at those options, the best data for those patients with bulky disease would be with rucaparib in this instance.

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