Platinum-resistant ovarian cancer

Resistance is defined by progression during platinum chemotherapy (refractory) or within six months of the last dose, though the boundary is arbitrary and the platinum-free interval is a continuum. Resistant tumours have usually restored DNA repair through BRCA reversion mutations, lost the drug-uptake pathways or acquired other changes after several lines of treatment, and prior PARP inhibitor exposure adds a further layer of cross-resistance. Symptoms come from peritoneal disease, bowel obstruction and ascites, and management is palliative in intent: control of disease, preservation of quality of life and, where possible, prolongation of survival. Single-agent weekly paclitaxel, pegylated liposomal doxorubicin, topotecan or gemcitabine each produce responses in roughly one patient in ten; AURELIA showed in 2014 that adding bevacizumab to any of them improves progression-free survival and symptom control, which became the standard for bevacizumab-naive patients.

MIRASOL was the first phase 3 trial to improve survival in this state with a new drug. Mirvetuximab soravtansine, an antibody-drug conjugate against folate receptor alpha, was compared with investigator's choice chemotherapy in women whose tumours expressed the receptor highly and who had had one to three prior lines; median overall survival was 16.46 months against 12.75, a hazard ratio of 0.67, with progression-free survival of 5.62 against 3.98 months and less haematological toxicity, though blurred vision and keratopathy require eye examinations and steroid drops. ROSELLA then tested relacorilant, a glucocorticoid receptor antagonist that reverses cortisol-driven chemoresistance, with nab-paclitaxel against nab-paclitaxel alone and extended median survival from 11.9 to 16.0 months, a hazard ratio of 0.69. KEYNOTE-B96 added pembrolizumab to weekly paclitaxel with or without bevacizumab and extended median survival in tumours with a combined positive score of one or more from 14.0 to 18.2 months, a hazard ratio of 0.76. Relacorilant and pembrolizumab both gained approvals in 2026.

The pipeline is dominated by antibody-drug conjugates: raludotatug deruxtecan against CDH6 in REJOICE-Ovarian01, rinatabart sesutecan and luveltamab tazevibulin against folate receptor alpha in RAINFOL-01 and other trials, and agents against B7-H4 and TROP2, with the question of how to sequence them when they share payloads. Secondary surgery has no role, hyperthermic intraperitoneal chemotherapy is unproven here, and hormonal therapy has a small place in low-grade and receptor-positive tumours. Early palliative care, management of malignant bowel obstruction and honest discussion of goals remain the core of care for a state that is still incurable.