Advanced High-Grade Serous Ovarian Cancer
Sequencing for newly diagnosed advanced high-grade serous ovarian cancer: platinum-taxane induction (with or without bevacizumab), then homologous-recombination-guided maintenance (olaparib for BRCA-mutant, olaparib + bevacizumab for HRD-positive, niraparib for HR-proficient), followed by platinum-sensitivity-guided therapy at relapse.
1L: Carboplatin + paclitaxel ± bevacizumab
Platinum-taxane induction after maximal cytoreductive surgery (primary or interval). Add bevacizumab for high-risk disease (stage IV, residual disease); it is then continued into maintenance. Obtain germline and somatic BRCA plus HRD testing to plan maintenance.
- Response to platinum → Homologous-recombination status after platinum response?
Homologous-recombination status after platinum response?
- BRCA-mutant → Olaparib maintenance
- HRD-positive (BRCA wild-type) → Olaparib + bevacizumab maintenance
- HR-proficient / biomarker-negative → Niraparib maintenance
maintenance: Olaparib maintenance
BRCA1/2 mutation (germline or somatic) after response to platinum-based therapy. Sustained progression-free survival benefit; monitor CBC for cytopenias and rare MDS/AML.
Evidence: SOLO-1
- Progression → Platinum-free interval at relapse?
maintenance: Olaparib + bevacizumab maintenance
HRD-positive, BRCA-wild-type disease already receiving bevacizumab. Monitor for hypertension, proteinuria, and PARP-inhibitor cytopenias.
Evidence: PAOLA-1
- Progression → Platinum-free interval at relapse?
maintenance: Niraparib maintenance
Option for HR-proficient / biomarker-negative disease (all-comers benefit, largest in HRD-positive). Use individualized (weight- and platelet-based) starting dose; monitor for thrombocytopenia.
- Progression → Platinum-free interval at relapse?
Platinum-free interval at relapse?
- Platinum-sensitive (≥6 mo) → Platinum-based doublet (carboplatin + gemcitabine or liposomal doxorubicin) ± bevacizumab
- Platinum-resistant (<6 mo) → Non-platinum single agent (liposomal doxorubicin, weekly paclitaxel, or topotecan) ± bevacizumab
2L: Platinum-based doublet (carboplatin + gemcitabine or liposomal doxorubicin) ± bevacizumab
Platinum-free interval ≥6 months. Re-challenge with a platinum doublet; consider secondary cytoreduction in selected patients and PARP-inhibitor maintenance if not previously used.
2L: Non-platinum single agent (liposomal doxorubicin, weekly paclitaxel, or topotecan) ± bevacizumab
Platinum-free interval <6 months. Sequential single agents; adding bevacizumab improves progression-free survival (AURELIA). Prioritize a clinical trial and consider mirvetuximab soravtansine for FRα-high disease.