Genetic Testing and Frontline Therapy in Ovarian Cancer

Bradley J. Monk, MD, FACOG, FACS:It’s important that the goal of frontline treatment of ovarian cancer, including surgery and chemotherapy, is long-term disease-free survival—tumor control, if you will. It’s not enough to help a patient live, you have to help her live well. And it all starts with a complete resection and surgery. This patient didn’t have that, but she did have an operation. It also begins with good chemotherapy, which is intravenous carboplatin and paclitaxel. This woman had intraperitoneal chemotherapy. Intraperitoneal chemotherapy is not better, it’s just more toxic. And the goal again is long-term disease-free survival and symptom-free survival. The average time to progression would be maybe 15 to 20 months. As I said, patients with aBRCAmutation can even do better than that becauseBRCAmutation portends an improved prognosis. The other thing that’s interesting about her is that she should have breast screening, probably breast MRI. She doesn’t necessarily need a risk-reducing mastectomy. Her family members should be tested because that’s the cure of ovarian cancer, identifying family members who have the genetic mutation and doing the risk-reducing surgery, which is removing the ovaries and fallopian tubes at the end of childbearing but before the risk increases for ovarian cancer, maybe before age 40, and that’s the “Angelina Jolie effect.” Angelina’s mom had died of ovarian cancer, but she won’t because she was tested forBRCAand had a risk-reducing operation.

One of the questions in the frontline management of advanced ovarian cancer certainly is intraperitoneal versus intravenous chemotherapy, and we touched on that, that we basically live in an IV world, not an IP world. But, also, should targeted therapy be added to frontline treatment? As you may be aware, in 2011, we published, in theNew England Journal of Medicine, GOG protocol 218. Robert Berger was the first author. We showed an improvement in progression-free survival, and that led to approval around the world of frontline bevacizumab. It was never submitted to the US FDA for frontline approval until August of 2017. It has a PDUFA (Prescription Drug User Fee Act) due date in June. So, we eagerly await the FDA’s decision as to whether or not bevacizumab should be added to frontline chemotherapy, and it’s not just during chemotherapy, it’s also in maintenance for a total time of 15 months, which is the average time of time to recurrence. We eagerly await the FDA’s decision because I think certainly that will change reimbursement. Currently, maybe 20% to 30% get frontline bevacizumab off-label, but it’s likely that that will increase with the approval, should it happen. And the due date, the PDUFA date, is June 25, 2018.

Transcript edited for clarity.

Platinum-Sensitive Recurrent Ovarian Cancer

September 2014

• A 40-year old Caucasian female presented to her gynecologist with abdominal pain and increased urinary urgency and frequency
  • PMH: unremarkable
  • FH: mother died of breast cancer at age 46
  • PE: tenderness in abdominal right lower quadrant; shifting dullness on abdominal palpation and percussion
  • Ultrasound: Abdominal and pelvic ultrasound showed a right-sided solid pelvic mass and ascites
• The patient was then referred to a gynecologic oncologist
  • Genetic testing was positive for BRCA1 mutation
  • Abdominal/pelvic CT findings showed a 5-cm x 2.5 cm x 3-cm right pelvic mass; ascites and omental cake was noted
  • CA125, 998 U/mL
• Biopsy findings showed stage 3C epithelial ovarian cancer
• Hysterectomy, bilateral salpingo-oophorectomy, and omentectomy was performed and optimal debulking was achieved (residual disease <1 cm)
• Treatment was initiated with IV/IP carboplatin/paclitaxel
  • After 6 cycles of therapy, CA-125 level declined to 9.3 U/ml.
  • Chemotherapy was tolerated well and without any unexpected toxicities

November 2016

• The patient reported feeling bloated and exhausted
• CT scan confirmed disease recurrence with ascites
• She was treated with carboplatin/paclitaxel/bevacizumab for 6 cycles and had a good response to therapy
• Following completion, she was continued on maintenance bevacizumab
• She continued to show improved response

January 2018

• The patient reported back with complaints of weight loss and abdominal distension
• CT scan revealed presence of small diffuse intraperitoneal masses