A 58-year-old woman from Bangalore is diagnosed with Stage IIB serous epithelial ovarian cancer after exploratory laparotomy. She has no residual disease after optimal cytoreduction. Molecular testing reveals she is BRCA1 wild-type, and her tumor shows low homologous recombination deficiency (HRD) score. She receives 6 cycles of carboplatin–paclitaxel chemotherapy and achieves complete clinical response. CA-125 normalizes to <10 U/mL. Which of the following is the most appropriate maintenance therapy strategy for this patient?

Explanation

## Maintenance Therapy in Epithelial Ovarian Cancer: HRD-Negative Disease **Key Point:** In patients with **HRD-negative, BRCA wild-type epithelial ovarian cancer** who achieve complete response to platinum–taxane chemotherapy, **bevacizumab monotherapy** is the most evidence-based maintenance strategy. PARP inhibitors are reserved for HRD-positive or BRCA-mutated tumors. ### Maintenance Therapy Algorithm by Molecular Status ```mermaid flowchart TD A[Epithelial Ovarian Cancer<br/>Complete Response to Chemo]:::outcome A --> B{BRCA-mutated<br/>or HRD-positive?}:::decision B -->|Yes| C[PARP inhibitor<br/>maintenance<br/>3 years]:::action B -->|No| D{High-risk<br/>features?}:::decision D -->|Yes<br/>Stage III/IV| E[Bevacizumab<br/>15 months]:::action D -->|No<br/>Early stage| F[Observation or<br/>bevacizumab<br/>per PARP trial]:::action C --> G[Superior PFS<br/>and OS vs observation]:::outcome E --> H[Improved PFS<br/>vs observation]:::outcome ``` ### Maintenance Therapy Comparison by Molecular Status | Molecular Status | Recommended Maintenance | Evidence | Duration | Benefit | |------------------|------------------------|----------|----------|----------| | **BRCA-mutated (germline or somatic)** | PARP inhibitor (olaparib, rucaparib) | SOLO2, ARIEL3 | 3 years | OS benefit (median ~3 years PFS gain) | | **HRD-positive (BRCA-WT)** | PARP inhibitor | SOLO1, ARIEL3 | 3 years | OS benefit (~2 years PFS gain) | | **HRD-negative, BRCA-WT (THIS CASE)** | **Bevacizumab monotherapy** | GOG-218, ICON7 | 15 months | PFS improvement (~3–4 months); OS benefit in some subgroups | | **HRD-negative, early stage** | Observation or bevacizumab | ICON7 subgroup | — | Bevacizumab may offer modest benefit | **High-Yield:** The **SOLO1 trial** (PARP inhibitor olaparib in BRCA-mutated) and **ARIEL3 trial** (PARP inhibitor rucaparib in HRD-positive) showed dramatic OS benefits. However, **PARP inhibitors are NOT indicated in HRD-negative disease** because the homologous recombination repair deficiency is the mechanism of PARP sensitivity. ### Why This Patient Gets Bevacizumab, Not PARP Inhibitor **Clinical Pearl:** This patient has: - **BRCA1 wild-type** → no germline BRCA mutation - **Low HRD score** → no somatic homologous recombination deficiency - **Stage IIB** (high-risk) → benefits from bevacizumab per GOG-218 and ICON7 Bevacizumab (anti-VEGF) is the standard of care in this molecular and clinical context. It improves progression-free survival by ~3–4 months and may provide overall survival benefit in Stage III/IV disease. **Key Point:** PARP inhibitors work by **synthetic lethality** in HRD-positive cells (BRCA-mutated or somatic HR-deficient). In HRD-negative tumors, the cells retain intact homologous recombination capacity and can repair PARP-induced DNA damage, rendering PARP inhibitors ineffective. ### Treatment Timeline for This Patient 1. **Carboplatin–paclitaxel** (6 cycles) → Complete response ✓ 2. **Bevacizumab maintenance** (15 months) → Improves PFS 3. **Surveillance** → CA-125, imaging, clinical exam every 3 months 4. **Recurrence management** → Platinum rechallenge ± bevacizumab if platinum-sensitive **Mnemonic:** **HRD-PARP rule**: - **H**RD-positive or **B**RCA-mutated → **PARP** inhibitor - **H**RD-negative → **B**evacizumab (or observation)