What are the treatment options for recurrent metastatic cervical cancer?

Treatment Options for Recurrent Metastatic Cervical Cancer

The preferred first-line treatment for recurrent metastatic cervical cancer is paclitaxel-cisplatin-bevacizumab, which significantly improves overall survival compared to chemotherapy alone. 1

First-Line Systemic Therapy Options

Preferred Regimens

• Paclitaxel-Cisplatin-Bevacizumab (Category 1)

  • Cisplatin 50 mg/m² on day 2
  • Paclitaxel 135 mg/m² over 24 hours on day 1
  • Bevacizumab 15 mg/kg every 3 weeks 1, 2

• Carboplatin-Paclitaxel-Bevacizumab (Category 2A)

  • Alternative for patients who cannot tolerate cisplatin
  • Carboplatin AUC 5 on day 1
  • Paclitaxel 175 mg/m² over 3 hours on day 1
  • Bevacizumab 15 mg/kg every 3 weeks 1

Other Recommended Regimens

• Cisplatin-Paclitaxel 3
• Carboplatin-Paclitaxel 3
• Cisplatin-Vinorelbine 3
• Cisplatin-Gemcitabine 3
• Cisplatin-Topotecan 3

Patient Selection Considerations

• For patients with good performance status (ECOG 0-1), combination therapy with bevacizumab is preferred 1
• Patients with prior platinum exposure may benefit from carboplatin-based regimens 1
• For PD-L1 positive tumors (CPS≥1), pembrolizumab with chemotherapy with or without bevacizumab should be considered 3

Second-Line Therapy Options

For patients who progress after first-line therapy, the following options are recommended:

• Pembrolizumab (for PD-L1 positive tumors that progressed on or after chemotherapy) 3
• Cemiplimab (included as a second-line option based on efficacy shown in cervical cancer) 3
• Single-agent options:
  • Paclitaxel 3
  • Erlotinib (category 2B) 3
  • Cisplatin-Gemcitabine (category 2B) 3

Locoregional Treatment Options

For patients with localized recurrence:

• Surgical resection should be evaluated for isolated recurrences 3
• Radiation therapy with or without concurrent chemotherapy for patients who have not received prior RT 3
• For patients with vulva-confined recurrence who previously received radiation, partial or total radical vulvectomy may be indicated 3

Management Algorithm

1. Assess disease extent and prior treatments:

   • If isolated recurrence and no prior RT: Consider surgical resection or RT with concurrent chemotherapy
   • If distant metastases or prior pelvic RT: Proceed to systemic therapy

2. PD-L1 testing:

   • If PD-L1 positive (CPS≥1): Consider pembrolizumab-containing regimens
   • If PD-L1 negative: Standard chemotherapy options

3. First-line systemic therapy selection:

   • Preferred: Paclitaxel-Cisplatin-Bevacizumab
   • If cisplatin intolerant: Carboplatin-Paclitaxel-Bevacizumab

4. Monitor for response:

   • Clinical examination every 3 months for first 2 years
   • Imaging studies (CT chest/abdomen/pelvis) every 2-3 months 1

5. Upon progression:

   • Switch to second-line therapy options
   • Consider clinical trial enrollment

Special Considerations

Bevacizumab-Related Toxicities

Monitor for:

• Hypertension (25% grade 2 or higher)
• Venous thromboembolic events (8.2% grade 2 or higher)
• Fistula formation (8.6% grade 2 or higher) 1
• Withhold for at least 28 days prior to elective surgery and 28 days following major surgery 2

Immunotherapy Considerations

• For patients with MSI-H/dMMR tumors, pembrolizumab or dostarlimab may be considered 3
• Immune checkpoint inhibitor combinations (such as anti-PD-1 plus anti-CTLA-4) are being investigated and show promising results 3

Prognosis

The prognosis for recurrent cervical cancer with distant metastases remains poor, with:

• Median overall survival of 12-17 months
• Median progression-free survival of 5-6 months 1

The addition of bevacizumab to chemotherapy has improved median overall survival from 13.3 to 16.8 months in this population 1.