Approaching Frontline Therapy Options for Ovarian Cancer

Shannon Westin, MD:The patient ultimately did haveBRCAtesting and was noted to have aBRCA1mutation in the germline setting. Given her no gross residual disease status, she was treated with IV [intravenous] and IP [intraperitoneal] chemotherapy with paclitaxel and cisplatin. She received a total of 6 cycles of treatment, and her imaging at the completion of treatment was completely negative and her CA 125 did normalize to 15 U/mL.

There are multiple options for adjuvant therapy after the completion of upfront surgery for patients with high-grade epithelial ovarian cancer. This particular patient received intraperitoneal chemotherapy, which is one of those options. There’s also the opportunity to use only IV chemotherapy, and that can be given in a number of ways. One way is to give both paclitaxel and carboplatin once every 3 weeks intravenously. Another option is to give something called dose-dense therapy, which is when paclitaxel is given weekly and carboplatin is given every 3 weeks. And finally, there’s also fractionated chemotherapy, where both drugs are given once a week just to spread them out and to reduce the toxicity.

Now, in regard to efficacy, we’ve had a number of different studies get reported favoring each one of these regimens, and we’re still learning as we go. It does appear that IV every 3 weeks can remain the standard of care, and it is certainly something that all patients can receive with good outcome. However, there are some studies that indicate in patients for whom you’re able to achieve no gross residual disease and optimal surgery—like the one this patient had—there can be a benefit as far as progression-free and overall survival in patients who are treated with intraperitoneal chemotherapy. So, that’s ultimately what this patient was treated with; that’s what her surgeon thought would be the optimal option. At the completion of therapy of 6 cycles, she had evidence of a complete clinical response, both by her imaging as well as her CA 125. I would say this is an absolutely optimal outcome for this patient.

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