Newly Diagnosed Advanced Ovarian Cancer: Treatment Overview

Bradley J. Monk, MD, FACOG, FACS:Many patients with newly diagnosed advanced ovarian cancer are treated by medical oncologists, and that’s OK. Many gynecologic oncologists do not give chemotherapy, and as such, they collaborate with a medical oncologist. There are others, like me, gynecologic oncologists who are surgeons but also give chemotherapy. This patient though has to, in combination with the provider, make some critical decisions as to what the appropriate chemotherapy should be. And there are 3 questions. Number 1, Should she receive intraperitoneal chemotherapy? Number 2, Should the paclitaxel be given weekly, perhaps even in a dosage-dense fashion, which would be 80 mg/m²every week without a break. Third is deciding whether targeted therapy should be given—either bevacizumab given with the chemotherapy and then in maintenance, or olaparib, a PARP inhibitor, just in maintenance.

How do you make those decisions? Personally, I think the most recent intraperitoneal chemotherapy study, which isolated the role of the intraperitoneal administration, did not confirm the value of intraperitoneal chemotherapy. As such, intraperitoneal chemotherapy is practiced less and less. Secondly, dosage-dense weekly paclitaxel used to be very common based on a Japanese trial. However, as that trial has become clear and tried to be confirmed in the more European sort of ethnicity, it cannot be confirmed with bevacizumab as in GOG-0262 with Dr John Chan in theNew England Journal of Medicine, or in Europe with ICON8.

So again, the pendulum has shifted away from intraperitoneal chemotherapy and also away from dosage-dense weekly chemotherapy, making the most common chemotherapy backbone intravenous, every 3 weeks, carboplatin, generally at an AUC [area under the concentration time curve] of 6, although some use 5, and paclitaxel delivered over 3 hours at 175 mg/m². Every 3 weeks, intravenous carboplatin and paclitaxel. Again, that’s the most common regimen.

What are the nuances? The nuances are targeted therapy. On June 13, 2018, bevacizumab was added to intravenous chemotherapy as an FDA-approved option, again given with chemotherapy after surgery for a total of 15 months. And then on December 19, 2018, only inBRCA-mutated patients, whether there was a germline mutation or a somatic mutation, giving olaparib, an oral PARP inhibitor, for 2 years in maintenance.

How would an oncologist decide whether to add targeted therapy to the frontline treatment of advanced newly diagnosed ovarian cancer? I think it’s easy because the use of olaparib is restricted and indicated based on germline and somaticBRCAmutations. Obviously ASCO [the American Society of Clinical Oncology], NCCN [the National Comprehensive Cancer Network], and the Society of Gynecologic Oncology recommends germline testing in all patients. We have to operationalize the somatic testing of the tumor because that’s an opportunity in about 5% to 10% of patients. So if you take that 5% to 10% of the somatic patients and the 15% to 20% of the germline patients, that’s a quarter of patients with aBRCAmutation who can receive frontline olaparib in maintenance for 2 years and can increase the progression-free survival by almost 36 months—SOLO-1,New England Journal of Medicine, Dr Katie Moore.

What about bevacizumab in the frontline? Bevacizumab in frontline newly diagnosed advanced ovarian cancer is based on 2 studies: GOG-0218 published by Dr Robert Burger in theNew England Journal of Medicinein December 2011, and ICON7, which was published by Dr Timothy Perren in the same issue of theNew England Journal of Medicine. The Burger trial, GOG-0218, was placebo controlled. It used bevacizumab, again with chemotherapy, started on the second dose at 15 mg/kg and in maintenance.

How do you decide when to use bevacizumab? Well, again, it’s indicated after surgery for all comers with advanced disease. But in order to enroll on GOG-0218, you had to have residual disease. Many individuals would think that the most exaggerated benefit would be in patients with large-volume residual disease or stage IV disease. And that’s supported both in the Dr Burger, GOG-0218 trial and in the Dr Perren, ICON7 trial. So in this particular patient who had large-volume residual disease, many practitioners would again begin carboplatin-paclitaxel with the first dose, add bevacizumab at 15 mg/kg on the second dose, continuing it in cycles 2 through 6, and then continuing single-agent bevacizumab in maintenance for a total of 15 months or 22 cycles.

Transcript edited for clarity.

Case: A 54-Year-Old Woman Diagnosed With Advanced Ovarian Cancer

H & P

• A 54-year-old woman presents after referral from her gynecologist for widespread tenderness, abdominal discomfort, and urinary symptoms. Pelvic exam performed by the gynecologist revealed a suspicious mass on her right ovary.
• Postmenopausal with two children
• PE: reveals an obese woman (BMI = 31 kg/m²) with mild hypertension and pre-diabetes; abdomen shows dullness to percussion
  • BP = 130/85 mm Hg
  • Fasting glucose = 115 mg/dL
  • Waist: hip ratio = 0.90

Imaging

• CT with contrast of the pelvis, abdomen, and chest reveals widespread peritoneal lesions and abdominal lymph node involvement
• Malignant ascites present

Biopsy and labs:

• Pathology, high-grade serous adenocarcinoma, ovarian primary
• BRCA1/2 status: negative
• CA-125: 785 U/mL

Treatment

• She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking; residual disease after cytoreduction = 1.1 cm
• Diagnosis, stage IIIC ovarian cancer, grade 3
• Started on every-3-week carboplatin and paclitaxel IV plus bevacizumab every 3 weeks