What is the recommended first-line systemic therapy for ovarian cancer management?

Ovarian Cancer Management and Systemic Therapy

First-Line Systemic Therapy

The standard first-line systemic therapy for advanced ovarian cancer is carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) administered intravenously every 3 weeks for six cycles. 1

Standard Chemotherapy Regimens

Primary treatment options include:

• Paclitaxel 175 mg/m² IV over 3 hours followed by carboplatin AUC 5-6 IV on Day 1, repeated every 3 weeks for 6 cycles (Category 1 recommendation) 1
• Docetaxel 60-75 mg/m² IV followed by carboplatin AUC 5-6 IV on Day 1, repeated every 3 weeks for 6 cycles (Category 1) 1
• Dose-dense paclitaxel 80 mg/m² IV on Days 1,8, and 15 with carboplatin AUC 6 IV on Day 1, repeated every 3 weeks for 6 cycles (Category 1) 1

For frail or elderly patients, weekly chemotherapy with paclitaxel 60 mg/m² and carboplatin AUC 2 can be considered as an alternative, offering better tolerability with lower rates of neuropathy, neutropenia, and alopecia 1, 2

Bevacizumab-Containing Regimens

Bevacizumab improves progression-free survival in stage III-IV ovarian cancer and should be considered in addition to standard chemotherapy (ESMO-MCBS score: 3; score 4 in high-risk patients) 1, 3

Two bevacizumab regimens are recommended:

• Paclitaxel 175 mg/m² IV, carboplatin AUC 6 IV, and bevacizumab 7.5 mg/kg IV on Day 1, repeated every 3 weeks for 5-6 cycles, followed by bevacizumab maintenance for up to 12 additional cycles (Category 3) 1
• Paclitaxel 175 mg/m² IV and carboplatin AUC 6 IV on Day 1 for 6 cycles, with bevacizumab 15 mg/kg IV starting on Day 1 of cycle 2, continued every 3 weeks for up to 22 cycles (Category 3) 1, 3

Intraperitoneal (IP) Chemotherapy

For selected stage III patients with optimally debulked disease (residual disease ≤1 cm), IP chemotherapy is recommended (Category 1), as evidence suggests a significant survival advantage 1

IP regimen:

• Paclitaxel 135 mg/m² IV over 24 hours on Day 1, followed by cisplatin 100 mg/m² IP on Day 2, and paclitaxel 60 mg/m² IP on Day 8 (max BSA 2.0 m²), repeated every 3 weeks for 6 cycles (Category 1) 1

Important caveat: IP chemotherapy and HIPEC are controversial and not considered standard of care in first-line treatment 1

Maintenance Therapy

Maintenance treatment with PARP inhibitors, with or without bevacizumab, is recommended based on molecular tumor characteristics:

For BRCA1/2-Mutated Tumors (germline or somatic):

• Olaparib for 2 years (ESMO-MCBS score: 4; ESCAT score: I-A) 1
• Niraparib for 3 years (ESMO-MCBS score: 3; ESCAT score: I-A) 1
• Olaparib plus bevacizumab for 2 years (ESMO-MCBS score: 3; ESCAT score: I-A) 1, 3

For BRCA1/2-Wild-Type/HRD-Positive Tumors:

• Niraparib for 3 years (ESMO-MCBS score: 3; ESCAT score: I-A) 1
• Olaparib plus bevacizumab for 2 years (ESMO-MCBS score: 3; ESCAT score: I-A) 1, 3

For HRD-Negative Tumors:

• Bevacizumab maintenance (Level I, A evidence) 1, 3
• Niraparib for 3 years (Level I, B evidence; ESMO-MCBS score: 3) 1

For Low-Grade Serous Carcinoma:

• Maintenance with anti-estrogen therapy after first-line platinum-based chemotherapy can be considered (Level IV, B evidence) 1

Neoadjuvant Chemotherapy Setting

For patients undergoing neoadjuvant chemotherapy followed by interval cytoreductive surgery:

• The same carboplatin-paclitaxel regimen is used 1
• Bevacizumab can be considered in the neoadjuvant setting (Level II, B evidence) 1, 3
• When interval cytoreductive surgery is not possible and there is no disease progression, three additional cycles of paclitaxel-carboplatin with bevacizumab are recommended 3

Recurrent Disease Management

Surgery for Relapse

Secondary cytoreductive surgery should be considered for first relapse >6 months after completion of platinum-based chemotherapy in patients with:

• Complete resection at primary surgery (or FIGO stage I-II)
• Good performance status (ECOG 0)
• Absence of ascites (<500 ml)

This AGO score predicts 76% likelihood of achieving complete resection and demonstrates benefit in overall survival and progression-free survival 1

Systemic Therapy for Recurrent Disease

The traditional 6-month platinum-free interval cut-off has been discontinued in clinical practice, as many factors influence treatment-free interval and response to platinum, including histotype and BRCA1/2 mutation status 1

For platinum-sensitive recurrent disease:

• Bevacizumab (15 mg/kg) can be combined with carboplatin and gemcitabine or carboplatin and paclitaxel, followed by bevacizumab maintenance 3
• Platinum-based combinations demonstrate activity even in patients with treatment-free interval <6 months 1

For platinum-resistant recurrent disease:

• Bevacizumab can be combined with paclitaxel, pegylated liposomal doxorubicin, or topotecan for patients who received ≤2 prior chemotherapy regimens 3

Key Clinical Considerations

Carboplatin dosing: Carboplatin has equivalent efficacy to cisplatin when given at a 4:1 dose ratio, with less non-hematological toxicity but greater hematological toxicity 1

Optimal cycle number: Available data does not support a benefit in overall survival from giving more than six courses of chemotherapy 1

Bevacizumab activity: Bevacizumab has shown activity in all histological subtypes of ovarian cancer, including less chemotherapy-responsive types like low-grade serous carcinoma and clear cell carcinoma 3

Common pitfall: Avoid external beam abdomino-pelvic radiotherapy and intraperitoneal brachytherapy in first-line treatment of advanced disease where there is residual disease after surgery, as they have no established role 1