Recurrent Ovarian Cancer: Selecting Second-Line Therapy

Shannon Westin, MD:Ultimately, this patient had no evidence of disease for approximately a year and a half, but then was found to have a recurrence. She presented with increasing abdominal pain, nausea, and early satiety. Her CA 125 level was found to be elevated at 203 U/mL, and subsequent imaging demonstrated recurrence in the peritoneal cavity with carcinomatosis as well as some enlarged lymph nodes.

She was counseled and treated with gemcitabine and carboplatin intravenously. She received a total of 6 cycles and had evidence of another complete response. So, there was no evidence of disease on imaging and she had a resolution of her CA 125 level down to about 11 U/mL. Her physicians counseled her and there was an opportunity for this patient to participate on a clinical trial of rucaparib, which is a PARP inhibitor, in the maintenance setting. She was treated with the rucaparib in the maintenance setting and tolerated it very well. She was on it for approximately 2 years without any evidence of disease.

During the rucaparib maintenance therapy, approximately 2 cycles in, the patient was noted to have an elevation in her liver enzymes. Her AST was 127 U/L and her ALT was 142 U/L. She underwent appropriate workup, and these lab values were found to come down on their own without any further therapy. There did not appear to be any liver damage. Her total bilirubin remained normal the entire time, so she was able to stay on the rucaparib therapy for over 2 years with a nice response.

When you have a patient with platinum-sensitive recurrent disease, one of the first questions that comes to mind is, can this patient have a secondary cytoreductive surgery? In this particular patient, her disease spread pattern was such that secondary cytoreductive surgery would likely not be beneficial. The patients we look for regarding surgery in this setting generally have 1, maybe 2, sites of disease. Certainly, this patient had a lovely platinum-free interval of about 18 months. That would make her likely to benefit from surgery. But the amount of disease that this particular patient had with the carcinomatosis as well as the lymph node involvement would make us not favor surgery in this setting.

Once surgery is off the table, we then discuss what type of therapy we are going to move forward with. Platinum-based doublet therapy is absolutely the standard of care for this type of patient. You have a lot of different options for what you can add to carboplatin in order to get a benefit that include paclitaxel, docetaxel, gemcitabine, and even pegylated liposomal doxorubicin. As far as we can tell, the outcomes are about the same for progression-free survival. There has been no impact on overall survival. What we do know is those doublets help get us a better response rate and a longer time before the cancer comes back.

Whenever you’re talking about the platinum-sensitive setting, you can also discuss with a patient the addition of bevacizumab, which is an antiangiogenic agent. That drug can be added to paclitaxel/carboplatin as well as to gemcitabine/carboplatin in the platinum-resistant recurrent setting. It does appear to increase response rates and potentially increase progression-free survival. An additional study demonstrated a potential benefit in overall survival when bevacizumab was added to paclitaxel and carboplatin.

Now comes the question of when you have this many options, how do you decide what a particular patient is going to receive? There’s a number of different factors. One is, what are their existing toxicities? Certainly, in a patient that has neuropathy, you may want to avoid paclitaxel. If a patient has difficulty going back and forth, if logistics are an issue, then you may want to consider something like pegylated liposomal doxorubicin, which is only given once a month. You’re going to use all of these different factors to try to home in and decide on what agent you’re going to use.

The addition of bevacizumab is another great question. You’re going to use existing information, not only toxicities but also past medical history. In a patient who has high blood pressure or hypertension that may be not well controlled, you certainly may avoid something like bevacizumab that can exacerbate that problem. And finally, for this particular patient, you have a patient who you know has aBRCAmutation. We know that we’ve got a number of different FDA-approved regimens for PARP inhibition; this particular patient was able to go on a clinical trial, which is always enticing. But the addition of a PARP inhibitor to maintenance therapy has to be considered as well. That’s a decision you make right when you’re deciding on your combination therapy.

Transcript edited for clarity.

A 49-Year-Old Woman with Platinum-Sensitive Epithelial Ovarian Cancer and GermlineBRCA1Mutation

March 2013

• A 49-year-old African American woman presented to her primary care physician complaining of abdominal bloating
• PMH: chronic HBV infection, mild HTN
• FH: mother died of breast cancer at age 59, cousin on mother’s side died of ovarian cancer at age 65
• CT, ascites and bilateral 8-cm adnexal masses
• CA 125, 285 U/mL
• She underwent exploratory laparotomy followed by omentectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, appendectomy, and resection of pelvic nodules
  • No gross residual disease (R0)
  • Germline molecular testing showed aBRCA1alteration
• Pathology: high grade epithelial ovarian cancer involving omentum, both ovaries, and 3 micro-metastatic lymph nodes
• She was treated with IV/IP paclitaxel/cisplatin; after completion, CA 125, 14.2, clinically NED

September 2015

• 18 months later, on routine follow up, CA 125, 203 U/mL
• Lymph node disease and carcinomatosis on imaging  
• She was treated with gemcitabine/carboplatin for 6 cycles
  • CA 125, 11.3; clinically NED
• The patient was started on rucaparib maintenance therapy while enrolled on a clinical trial
• After 2 cycles of therapy, the patient’s live enzymes rose transiently and then returned to normal
  • AST, 127 U/L
  • ALT, 142 U/L
  • Creatinine, 1.5 mg/d            

November 2017

• The patient complained of worsening fatigue and bloating
• CA 125, 1004 U/mL