What is the recommended use, dosing schedule, chemotherapy combination, maintenance strategy, safety monitoring, contraindications, and alternative options for bevacizumab in adult patients with recurrent platinum‑resistant epithelial ovarian, fallopian‑tube, or primary peritoneal cancer?

Bevacizumab in Platinum-Resistant Recurrent Ovarian Cancer

For platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab should be administered at 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks in combination with single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin, topotecan, or gemcitabine), followed by bevacizumab maintenance until disease progression or unacceptable toxicity. 1, 2

FDA-Approved Indication and Patient Selection

• Bevacizumab is FDA-approved for platinum-resistant recurrent disease in combination with paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan for patients who received ≤2 prior chemotherapy regimens. 1

• The approval specifically targets patients with recurrence within <6 months from the most recent platinum-based therapy. 2

• Critical exclusion criteria include evidence of recto-sigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction due to gastrointestinal perforation risk. 2

Dosing Schedule and Administration

Two dosing regimens are FDA-approved: 2

• 10 mg/kg IV every 2 weeks, or

• 15 mg/kg IV every 3 weeks

• Treatment continues until disease progression or unacceptable toxicity—there is no predetermined cycle limit for maintenance therapy. 2

• The European Society for Medical Oncology recommends the 15 mg/kg every 3 weeks dosing when combined with chemotherapy. 3

Chemotherapy Combination Options

Select ONE of the following single-agent chemotherapies to combine with bevacizumab: 1, 3, 4

• Paclitaxel (standard or weekly dosing)
• Pegylated liposomal doxorubicin (PLD)
• Topotecan
• Gemcitabine

The choice should prioritize quality of life and symptom control, as this is the primary treatment goal in platinum-resistant disease. 4

Maintenance Strategy

• After completing chemotherapy cycles, continue bevacizumab as single-agent maintenance therapy at the same dose and schedule used during combination therapy. 1

• In the pivotal MO22224 trial, 40% of patients on chemotherapy alone crossed over to receive bevacizumab upon progression, demonstrating the drug's continued utility even after initial progression. 2

• Bevacizumab maintenance continues until disease progression or unacceptable toxicity—no fixed duration is specified. 2

Safety Monitoring Requirements

Mandatory monitoring includes: 2

Hypertension

• Monitor blood pressure every 2-3 weeks during treatment
• Grade 3-4 hypertension occurred in 6.7% vs 1.1% (chemotherapy alone) in platinum-resistant patients 2
• Hypertension rates reach 11% in cervical cancer populations receiving bevacizumab 2

Proteinuria

• Perform urinalysis at baseline and before each dose
• Grade 2-4 proteinuria occurred in 12% vs 0.6% (chemotherapy alone) 2
• Renal thrombotic microangiopathy manifesting as severe proteinuria has been reported post-marketing 2

Hemorrhage

• Epistaxis is common (5% Grade 2-4 events) but usually manageable 2
• Serious hemorrhagic events (Grade ≥3) occurred in 2.3% of patients across indications 2

Gastrointestinal Perforation

• This is the most critical toxicity in ovarian cancer patients
• Anal fistula occurred in 4-6% of cervical cancer patients (vs 0% without bevacizumab) 2
• Intestinal necrosis, anastomotic ulceration, and gastrointestinal ulcers are reported post-marketing 2

Hematologic Toxicity

• Grade 2-4 neutropenia occurred in 31% vs 25% (chemotherapy alone) 2
• Monitor complete blood counts regularly

Other Monitoring

• Palmar-plantar erythrodysesthesia syndrome: 4.5% Grade 3-4 (vs 1.7% without bevacizumab) 2
• Peripheral sensory neuropathy: 18% Grade 2-4 (vs 7% without bevacizumab) 2

Absolute Contraindications

Do not use bevacizumab in patients with: 2

• Evidence of recto-sigmoid involvement on pelvic examination
• Bowel involvement documented on CT scan
• Clinical symptoms of bowel obstruction
• Recent history of gastrointestinal perforation or fistula

Efficacy Data in Platinum-Resistant Disease

• The MO22224 trial demonstrated improved progression-free survival with bevacizumab plus chemotherapy versus chemotherapy alone in platinum-resistant disease. 2

• Six-month progression-free survival rates of 56% have been reported with bevacizumab-containing regimens in this population. 5

• Bevacizumab has shown activity across all histological subtypes, including less chemotherapy-responsive types like low-grade serous and clear cell carcinoma. 3

• No predictive molecular biomarkers have been identified for bevacizumab efficacy—only clinical factors (stage, debulking status, presence of ascites) appear to have predictive utility. 4

Alternative Options and Sequential Therapy

If bevacizumab is contraindicated or not tolerated: 4

• Sequential single-agent non-platinum chemotherapy without bevacizumab remains standard
• Consider testing for folate receptor alpha (FRα) expression for mirvetuximab soravtansine eligibility (objective response rate 42.3% in FRα-high platinum-resistant disease) 4

For patients with BRCA mutations or homologous recombination deficiency (HRD):

• PARP inhibitors are not FDA-approved as monotherapy for platinum-resistant disease 1
• However, if the patient later achieves response to platinum rechallenge, PARP inhibitor maintenance becomes an option 1

Special Considerations for Heavily Pretreated Patients

• Despite FDA approval limiting use to ≤2 prior regimens, retrospective data suggest bevacizumab can be used safely in heavily pretreated patients (>3 prior regimens). 6

• Grade ≥3 toxicity rates did not differ significantly based on number of prior cytotoxic regimens. 6

• Median overall survival of 21 months from bevacizumab initiation has been reported in heavily pretreated populations. 6

Integration with Palliative Care

• Early palliative care integration is essential as it significantly improves quality of life, decreases symptom intensity, and possibly improves survival in platinum-resistant disease. 4

• The primary treatment goal shifts from cure to quality of life and symptom control in this population. 4

Common Pitfalls to Avoid

• Do not delay treatment for molecular profiling—routine comprehensive molecular profiling is not recommended (NCCN Category 3) and does not improve outcomes in platinum-resistant ovarian cancer. 4

• Do not use bevacizumab in patients with bowel involvement or obstruction symptoms—this dramatically increases perforation risk. 2

• Do not discontinue bevacizumab at a predetermined cycle number—continue until progression or toxicity. 2

• Do not assume all patients need dose reduction—the standard doses (10 mg/kg Q2W or 15 mg/kg Q3W) should be used unless toxicity mandates adjustment. 2