What is the role of Bevacizumab (bevacizumab) in upfront versus recurrent ovarian cancer treatment?

Bevacizumab in Upfront vs Recurrent Ovarian Cancer

Bevacizumab has a stronger and more established role in recurrent ovarian cancer compared to upfront treatment, where its use remains controversial with only a Category 3 recommendation (indicating >25% of NCCN panel members believe it is not appropriate). 1

Upfront Treatment: Limited Role with Significant Controversy

NCCN Position on First-Line Use

Most NCCN panel members believe bevacizumab should NOT be added to up-front chemotherapy in patients with ovarian cancer because GOG-0218 and ICON7 trials showed no statistically significant increase in overall survival and no improved quality of life. 1

Evidence from Upfront Trials

• GOG-0218 demonstrated only a modest 3.8-month increase in progression-free survival when bevacizumab was given with carboplatin/paclitaxel followed by maintenance, with no overall survival benefit. 1

• ICON7 showed an even smaller 1.7-month progression-free survival benefit with no mature overall survival data at the time of guideline publication. 1

• Quality of life was similar between treatment arms in both trials, providing no additional justification for upfront use. 1

Safety Concerns in Upfront Setting

The risk-benefit calculation is unfavorable upfront, with serious adverse events including:

• Gastrointestinal perforation or fistula in <3% of patients 1
• Cost considerations without clear mortality or quality of life benefit 1

If Bevacizumab Is Used Upfront (Category 3)

If clinicians choose to use bevacizumab despite the controversy, only specific regimens are recommended:

GOG-0218 regimen: Paclitaxel 175 mg/m² IV over 3 hours and carboplatin AUC 6 IV over 30 minutes Day 1, repeated every 3 weeks × 6 cycles. Starting Day 1 of cycle 2, give bevacizumab 15 mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. 1

ICON7 regimen: Paclitaxel 175 mg/m², carboplatin AUC 6, and bevacizumab 7.5 mg/kg IV Day 1, repeated every 3 weeks × 5-6 cycles, then continue bevacizumab for up to 12 additional cycles. 1

Recurrent Disease: Established and Preferred Role

Platinum-Resistant Recurrent Disease

Single-agent bevacizumab is recommended as a PREFERRED recurrence therapy for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. 1, 2

Evidence from MO22224 Trial

The FDA-approved indication for platinum-resistant recurrent disease is based on compelling evidence:

• Progression-free survival: 6.8 months with bevacizumab plus chemotherapy vs 3.4 months with chemotherapy alone (HR 0.38, p<0.0001) 3

• Overall response rate: 28% with bevacizumab plus chemotherapy vs 13% with chemotherapy alone 3

• Bevacizumab demonstrated a 21% response rate and is active in both platinum-sensitive and platinum-resistant patients. 1

Dosing for Recurrent Disease

Bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks in combination with single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). 3

Platinum-Sensitive Recurrent Disease

For platinum-sensitive recurrent disease (recurrence >6 months after primary treatment), platinum-based combination regimens remain the preferred first-line approach. 1, 2

Bevacizumab can be added to platinum-based combinations in the recurrent setting, with ongoing trials (OCEANS, AURELIA) assessing this approach. 1

Critical Safety Considerations Across All Settings

Patient Selection to Avoid Gastrointestinal Perforation

Exclude patients with:

• Clinical symptoms of bowel obstruction 4
• Evidence of rectosigmoid involvement on pelvic examination 4
• Bowel involvement on CT scan 4

This careful screening approach reduced gastrointestinal perforation rates from 11% in early trials to 0% in carefully selected patients. 4

Common Adverse Events Requiring Monitoring

Grade 3-4 adverse reactions occurring at higher incidence (≥2%) with bevacizumab in recurrent ovarian cancer:

• Hypertension (6.7% vs 1.1%) 3
• Palmar-plantar erythrodysesthesia syndrome (4.5% vs 1.7%) 3
• Proteinuria (12% vs 0.6%) 3
• Neutropenia (31% vs 25%) 3

Algorithm for Bevacizumab Use

For newly diagnosed advanced ovarian cancer:

• Do NOT routinely add bevacizumab to upfront carboplatin/paclitaxel 1
• Consider only in clinical trial settings or after extensive discussion of limited benefits vs risks 1

For recurrent platinum-resistant disease:

• USE bevacizumab 10 mg/kg every 2 weeks (or 15 mg/kg every 3 weeks) with single-agent chemotherapy as preferred therapy 1, 2, 3
• Screen carefully for bowel involvement before initiating 4

For recurrent platinum-sensitive disease:

• Prioritize platinum-based combination chemotherapy 1, 2
• Consider adding bevacizumab based on individual patient factors and ongoing trial data 1