Targeted Therapy in Newly Diagnosed Advanced Ovarian Cancer

Bradley J. Monk, MD, FACOG, FACS:One of the evolving areas of the treatment of advanced ovarian cancer is maintenance therapy. We have 3 PARP inhibitors—olaparib, rucaparib, and niraparib in maintenance, all comers, second and beyond-line therapy if a patient has a complete or partial response to a platinum. All comers: second-line oral niraparib, rucaparib, and olaparib. Now we have frontline maintenance PARP inhibitor olaparib but only inBRCApatients. And then we have frontline maintenance bevacizumab with chemotherapy, again up to 15 months.

The point is, we have 5 maintenance-targeted therapies. We have 3 PARP inhibitors in the second-line setting, 1 PARP inhibitor in the frontline, and bevacizumab. Maintenance is here to stay, and the reason it’s here to stay is for 3 reasons. One, it works. All those studies show important statistically significant and clinically important delays in progression-free survival. And, two, they’re relatively well tolerated. And, three, it’s convenient. So that’s the nuance of maintenance-targeted therapy in ovarian cancer. It works, it’s tolerable, and it’s convenient.

The use of targeted therapies in newly diagnosed advanced ovarian cancer has to be understood in the context of adverse effects. All anti-cancer therapies have toxicities. So let’s talk about the 2 categories: anti-angiogenics, or bevacizumab, and PARP inhibitors—in this case, olaparib forBRCA-mutated patients. The most common adverse event associated with bevacizumab is hypertension. Certainly, they can have proteinuria and other adverse effects, and we worry about GI [gastrointestinal] perforation. GI perforations can be mitigated and reduced if you start the second or even third cycle and if you avoid treatment or the use of bevacizumab in patients who have inflammatory bowel disease.

The adverse effects of olaparib and other PARP inhibitors are threefold: fatigue, and that can be managed with dose delays and dose reductions; bone marrow suppression, and sometimes even anemia and thrombocytopenia; and GI toxicities, particularly nausea, vomiting, and diarrhea. Again, they can be managed with supportive care, dose delays, and dose reductions. So we have to have a healthy respect for these targeted therapies. But with dose reductions, dose delays, and supportive care, and by managing the hypertension, if you will, with bevacizumab, or by managing the nausea and fatigue and bone marrow suppression with PARP inhibitors, these medications can be used with patients without a decrement in quality of life. All these studies have had questionnaires, or patient-reported outcome assessments, and there was no decrement.

There’s a lot of discussion about contraindications to bevacizumab. The easy ones are nonhealing wounds, deep venous thrombosis [DVT] that is not well controlled. Patients who have stable DVT are eligible for bevacizumab treatment but also, in our particular patient, hypertension. Because the most common serious adverse event is hypertension. So what we do is we certainly start it only if the hypertension is well controlled, and we ask the patient to monitor her blood pressure at home. And ultimately if she starts to have elevated blood pressure or hypertension, if you will, then we manage it. And it can be managed without altering the dosing regimen, frequently.

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