Platinum-Sensitive Recurrence in a BRCA Wild-Type, HRD-Negative Patient

A platinum-free interval of 14 months makes her platinum-sensitive.

Systemic therapy: the standard is a platinum doublet for six cycles. Carboplatin/paclitaxel is reasonable despite grade 1 neuropathy, with counselling that it may worsen; carboplatin/gemcitabine or carboplatin/liposomal doxorubicin are equally acceptable alternatives with less neurotoxicity if she wants to protect her nerves. Single-agent platinum is used when residual toxicity precludes a doublet. Bevacizumab can be added to the doublet and continued as maintenance if she has not previously received it; her hypertension must be controlled first.

Secondary cytoreduction: consider it only where complete resection is genuinely achievable. Validated selection criteria (ECOG 0, ascites under 500 mL, complete resection at primary surgery) fit her, and a randomized trial showed an overall survival benefit when complete resection was achieved; a North American trial was negative and confounded by uneven complete resection rates. Two small nodules in an asymptomatic patient can be resected or observed, but the operative decision should be made by an experienced surgeon before chemotherapy starts, not after.

She should not simply repeat 'the same chemo' by reflex; the choice depends on residual toxicity, prior bevacizumab exposure, and her goals.

PARP inhibitors are maintenance therapy given after a response to platinum, not salvage therapy for measurable, growing disease. Starting one now, with rising CA-125 and enlarging nodules, would be inappropriate.

Her tumor is BRCA wild-type and HRD-negative, so the expected benefit is much smaller than in BRCA-mutated disease. In the trial that established niraparib in recurrent platinum-sensitive disease, the non-germline-BRCA, HRD-negative subgroup had a hazard ratio around 0.58 with a median progression-free survival gain of only a couple of months. Olaparib maintenance has its strongest support in germline BRCA-mutated disease; tumor-agnostic indications apply to mismatch-repair deficiency, not to HRD-negative ovarian cancer.

The honest counselling points:

• The benefit is a modest delay in progression; a clear overall survival gain in HRD-negative disease has not been demonstrated.
• Toxicity is real: cytopenias requiring monitoring, hypertension (relevant for her), fatigue, pneumonitis, and a small risk of myelodysplastic syndrome or acute leukemia.
• A shared decision after she responds to platinum is legitimate; declining is also legitimate, and a clinical trial is a reasonable alternative.

Correct the misconception directly: no oral agent keeps ovarian cancer away indefinitely.

This is progression on a platinum doublet, so she is now platinum-resistant. Stop the platinum regimen and switch strategy rather than completing six cycles.

• Single-agent options: weekly paclitaxel, pegylated liposomal doxorubicin, gemcitabine, topotecan, or cyclophosphamide. Choice is driven by residual toxicity; her grade 1 neuropathy makes weekly paclitaxel less attractive and liposomal doxorubicin or gemcitabine more so.
• Bevacizumab: may be added to a single agent if not previously used and blood pressure is controlled, with attention to bowel involvement and perforation risk.
• Biomarker reconsideration: re-biopsy is worth considering, especially if she had a BRCA mutation with a possible reversion mutation, or to reassess HER2, folate receptor alpha, or mismatch-repair status for trial eligibility.
• Prior PARP exposure: if she had received a PARP inhibitor as maintenance earlier, there is no established role for rechallenge outside a trial.
• Goals: with platinum-resistant disease, median survival is limited; quality of life, symptom control, and early palliative care involvement should be integrated now, not deferred until later lines.

Also revisit whether the progression is genuine - confirm with imaging rather than CA-125 alone if the lesion is ambiguous.