Is there a role for adding bevacizumab to neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin in a patient with Stage 3c ovarian cancer of clear cell histology?

Bevacizumab in NACT for Stage 3C Clear Cell Ovarian Cancer

Adding bevacizumab to neoadjuvant chemotherapy with paclitaxel and carboplatin in stage 3C clear cell ovarian cancer is not recommended based on current evidence, as it provides no meaningful benefit in complete resection rates or progression-free survival while adding toxicity risk. 1

Evidence Against Bevacizumab in the NACT Setting

The most recent ESMO 2023 guidelines specifically address bevacizumab with NACT and conclude that the potential benefit of two to three doses of bevacizumab before interval cytoreductive surgery is debatable due to its lack of impact on complete resection rate and PFS. 1

Key Trial Data on NACT Plus Bevacizumab

Two randomized trials directly evaluated this question:

• ANTHALYA and GEICO 1205/NOVA trials both tested bevacizumab added to NACT (carboplatin/paclitaxel) before interval debulking surgery 1
• No increase in grade 3-4 toxicities was observed compared with chemotherapy alone 1
• Critical finding: No improvement in complete resection rates or PFS despite adding bevacizumab to the neoadjuvant regimen 1

Special Consideration for Clear Cell Histology

Clear cell carcinoma is a less chemoresponsive histotype compared to high-grade serous carcinoma, with multiple retrospective studies showing lower response rates to standard platinum-based chemotherapy 1

However, bevacizumab has shown activity in all histotypes including clear cell carcinoma 1, which theoretically could support its use. Despite this activity, the NACT trials showed no benefit even in mixed histology populations that included less responsive subtypes.

When Bevacizumab IS Indicated in First-Line Treatment

Bevacizumab is licensed at 15 mg/kg given for 15 months in combination with first-line paclitaxel-carboplatin chemotherapy for patients with stage IIIB-IV ovarian cancer, regardless of histology 1

The key distinction is timing and context:

• GOG-218 and ICON7 trials showed bevacizumab added to adjuvant (post-surgical) chemotherapy plus maintenance improved PFS by 3.8 months and 1.7 months respectively, though without OS benefit 1
• Post hoc analysis suggested greater benefit in "high-risk" populations (stage III with macroscopic residual tumor or stage IV disease) 1
• Your stage 3C patient would qualify as high-risk if there is anticipated macroscopic residual disease

Clinical Algorithm for Your Patient

For stage 3C clear cell ovarian cancer planned for NACT:

1. Do NOT add bevacizumab during the neoadjuvant phase (cycles 1-3 or 1-4 before surgery) 1

2. Administer standard carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) every 3 weeks for 3-4 cycles before interval debulking surgery 1

3. After interval cytoreductive surgery, IF the patient has high-risk features (stage IV disease or macroscopic residual tumor after surgery), then consider adding bevacizumab 15 mg/kg every 3 weeks starting with cycle 2 post-surgery, continuing through cycle 6, then as maintenance for up to 15 months total 1

4. If bevacizumab is used post-operatively, it must be started at least 4-6 weeks (preferably 6-7 weeks) after surgery to minimize surgical complication risk 2

Critical Safety Caveats

Bevacizumab carries significant toxicity risks that influenced NCCN's Category 3 recommendation (>25% of panel members believe it is not appropriate): 1, 3

• Gastrointestinal perforation or fistula in <3% of patients 1, 3, 4
• Hypertension requiring medical therapy in 16.5-22.9% of patients 4
• No quality of life improvement demonstrated in GOG-218 or ICON7 1, 3
• No overall survival benefit in the general population 1, 3

The magnitude of clinical benefit versus potential for serious side effects and cost makes routine upfront use controversial, particularly in the NACT setting where no benefit has been demonstrated 1, 3

Bottom Line for Your Case

Proceed with standard carboplatin-paclitaxel NACT without bevacizumab. 1 Reassess after interval debulking surgery, and if high-risk features are confirmed (macroscopic residual disease), then discuss adding bevacizumab to the adjuvant phase with the patient, acknowledging the modest PFS benefit, lack of OS benefit, and toxicity risks. 1, 3