{"entity":{"id":"platinum-resistant-ovarian-cancer","kind":"cancer","name":"Platinum-resistant ovarian cancer","aka":["Platinum-resistant recurrent ovarian cancer","Platinum-refractory ovarian cancer","Platinum-free interval under six months","PROC"],"tldr":"Platinum-resistant ovarian cancer grows back within six months of platinum chemotherapy, or during it, and used to be treated with single chemotherapy drugs that shrink a tumour one time in ten. The antibody-drug conjugate mirvetuximab soravtansine, the cortisol-blocking drug relacorilant and pembrolizumab in PD-L1-positive tumours have each extended survival in phase 3 trials since 2023.","summary":"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.\n\nMIRASOL 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.\n\nThe 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Ovarian_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ovarian_cancer"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"Every woman who relapses repeatedly eventually reaches this state, and about a quarter of advanced ovarian cancers are resistant from the start; median survival was around a year with single-agent chemotherapy, and it is where the first antibody-drug conjugate and the first new drug classes in a decade have arrived.","subtypes":["Platinum-refractory (progression during platinum)","Platinum-resistant relapse within six months","Folate receptor alpha-high (mirvetuximab soravtansine, MIRASOL)","PD-L1 combined positive score 1 or more (pembrolizumab with paclitaxel, KEYNOTE-B96)","Bevacizumab-naive (chemotherapy with bevacizumab, AURELIA)","Platinum-resistant after PARP inhibitor (cross-resistance)","High-grade serous and BRCA-reverted tumours (most cases)"],"biomarkers":["Platinum-free interval under six months","Folate receptor alpha immunohistochemistry (high expression required for mirvetuximab)","PD-L1 combined positive score (pembrolizumab)","Prior bevacizumab and PARP inhibitor exposure","CDH6, B7-H4 and TROP2 expression (antibody-drug conjugate trials)","BRCA reversion mutations","CA-125 and imaging for response"],"standardOfCare":[{"setting":"Folate receptor alpha-high","approach":"Mirvetuximab soravtansine with ophthalmic monitoring (MIRASOL).","refs":["mirvetuximab-soravtansine","mirasol","folr1","adc"]},{"setting":"PD-L1 CPS 1 or more","approach":"Pembrolizumab with weekly paclitaxel, with bevacizumab where not previously given (KEYNOTE-B96).","refs":["pembrolizumab","paclitaxel","bevacizumab","keynote-b96","pdl1"]},{"setting":"Any expression status","approach":"Relacorilant with nab-paclitaxel (ROSELLA); or single-agent weekly paclitaxel, pegylated liposomal doxorubicin, topotecan or gemcitabine with bevacizumab if bevacizumab-naive (AURELIA).","refs":["relacorilant","rosella","paclitaxel","pegylated-liposomal-doxorubicin","topotecan","gemcitabine","bevacizumab"]},{"setting":"Later lines","approach":"Clinical trials of antibody-drug conjugates against CDH6, folate receptor alpha, B7-H4 and TROP2; hormonal therapy in receptor-positive low-grade disease.","refs":["raludotatug-deruxtecan","rejoice-ovarian01","rinatabart-sesutecan","rainfol-01","luveltamab-tazevibulin","letrozole"]},{"setting":"Supportive care","approach":"Early palliative care, drainage of ascites, management of bowel obstruction and nutritional support alongside anticancer treatment.","refs":["ovarian"]}],"stateOfArt":["MIRASOL made mirvetuximab soravtansine the first drug to improve survival in platinum-resistant disease in a phase 3 trial.","ROSELLA introduced glucocorticoid receptor antagonism as a new mechanism, and KEYNOTE-B96 brought checkpoint inhibition into a disease that had resisted it.","A crowded pipeline of antibody-drug conjugates is redefining later-line treatment."],"history":[{"year":1996,"title":"Topotecan and later pegylated liposomal doxorubicin approved for relapsed ovarian cancer","refs":["topotecan","pegylated-liposomal-doxorubicin"]},{"year":2014,"title":"AURELIA: bevacizumab with chemotherapy improves progression-free survival in platinum-resistant disease","refs":["bevacizumab"]},{"year":2022,"title":"Mirvetuximab soravtansine accelerated approval after SORAYA","refs":["mirvetuximab-soravtansine"]},{"year":2023,"title":"MIRASOL: mirvetuximab soravtansine extends survival, 16.46 versus 12.75 months","refs":["mirasol"]},{"year":2025,"title":"ROSELLA: relacorilant with nab-paclitaxel extends survival, 16.0 versus 11.9 months","refs":["rosella","relacorilant"]},{"year":2025,"title":"KEYNOTE-B96: pembrolizumab with paclitaxel extends survival in PD-L1-positive disease","refs":["keynote-b96","pembrolizumab"]},{"year":2026,"title":"Relacorilant and pembrolizumab approved for platinum-resistant ovarian cancer","refs":["relacorilant","pembrolizumab"]}],"pipeline":["raludotatug-deruxtecan","rejoice-ovarian01","rinatabart-sesutecan","rainfol-01","luveltamab-tazevibulin","relacorilant","idea-fra-adc-sequencing-ovarian"],"openProblems":["Sequencing antibody-drug conjugates that share topoisomerase or tubulin payloads.","Whether platinum resistance can be reversed rather than bypassed.","A definition of resistance based on biology rather than a six-month clock."],"parent":"ovarian"},"route":"/cancers/platinum-resistant-ovarian-cancer/","neighbours":{"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"luveltamab-tazevibulin","kind":"drug","name":"Luveltamab tazevibulin","route":"/drugs/luveltamab-tazevibulin/"},{"id":"mirvetuximab-soravtansine","kind":"drug","name":"Mirvetuximab soravtansine","route":"/drugs/mirvetuximab-soravtansine/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pegylated-liposomal-doxorubicin","kind":"drug","name":"Pegylated liposomal 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Cancer(PANK","route":"/trials/nct06994195/"},{"id":"nct05128825","kind":"trial","name":"A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer","route":"/trials/nct05128825/"},{"id":"nct07546500","kind":"trial","name":"A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression","route":"/trials/nct07546500/"},{"id":"nct06434610","kind":"trial","name":"A Study of B013 in Combination With Paclitaxel in Patients With Platinum-resistant Recurrent Ovarian Cancer.","route":"/trials/nct06434610/"},{"id":"nct07023627","kind":"trial","name":"A Study of INCB123667 in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression","route":"/trials/nct07023627/"},{"id":"nct07042802","kind":"trial","name":"A Study of LBL-024 in Combination With Paclitaxel ± Bevacizumab for the Treatment of Platinum-resistant Ovarian Cancer","route":"/trials/nct07042802/"},{"id":"nct06828354","kind":"trial","name":"A Study of SHR-A1811 in Subjects With Ovarian Cancer","route":"/trials/nct06828354/"},{"id":"nct06682988","kind":"trial","name":"A Study to Assess Adverse Events and Change in Disease Activity in Participants With Platinum-Resistant Advanced High-Grade Epithelial Ovarian, Primar","route":"/trials/nct06682988/"},{"id":"nct07286266","kind":"trial","name":"A Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer (BEHOLD-Ovarian01)","route":"/trials/nct07286266/"},{"id":"nct07604766","kind":"trial","name":"An Extension Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Can","route":"/trials/nct07604766/"},{"id":"nct07218809","kind":"trial","name":"AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer","route":"/trials/nct07218809/"},{"id":"nct03949283","kind":"trial","name":"Cancer Stem Cell Assay Directed Chemotherapy in Recurrent Platinum Resistant Ovarian Cancer","route":"/trials/nct03949283/"},{"id":"nct06690775","kind":"trial","name":"CATALINA-2: A Clinical Study of TORL-1-23 in Platinum-resistant Ovarian Cancer.","route":"/trials/nct06690775/"},{"id":"nct04921527","kind":"trial","name":"Chiauranib Plus Weekly Paclitaxel in Patients with Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer","route":"/trials/nct04921527/"},{"id":"nct05281471","kind":"trial","name":"Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)","route":"/trials/nct05281471/"},{"id":"nct06303505","kind":"trial","name":"FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC","route":"/trials/nct06303505/"},{"id":"nct06855069","kind":"trial","name":"HS-20089 for Injection in Patients With Platinum-Resistant Recurrent Epithelial Ovarian Cancer","route":"/trials/nct06855069/"},{"id":"nct06014528","kind":"trial","name":"IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurren","route":"/trials/nct06014528/"},{"id":"nct06787612","kind":"trial","name":"Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer","route":"/trials/nct06787612/"},{"id":"keynote-b96","kind":"trial","name":"KEYNOTE-B96 / ENGOT-ov65","route":"/trials/keynote-b96/"},{"id":"mirasol","kind":"trial","name":"MIRASOL / GOG-3045","route":"/trials/mirasol/"},{"id":"nct05446298","kind":"trial","name":"ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer","route":"/trials/nct05446298/"},{"id":"nct05271318","kind":"trial","name":"Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) ","route":"/trials/nct05271318/"},{"id":"rainfol-01","kind":"trial","name":"RAINFOL-01 (Rina-S)","route":"/trials/rainfol-01/"},{"id":"rejoice-ovarian01","kind":"trial","name":"REJOICE-Ovarian01","route":"/trials/rejoice-ovarian01/"},{"id":"rosella","kind":"trial","name":"ROSELLA / GOG-3073","route":"/trials/rosella/"},{"id":"nct06394492","kind":"trial","name":"SHR-A1921 for Injection in Patients With Platinum-Resistant Recurrent Epithelial Ovarian Cancer","route":"/trials/nct06394492/"},{"id":"nct06834672","kind":"trial","name":"Study of IBI354 Versus Investigator's Choice of Chemotherapy in Patients With Platinum-resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer","route":"/trials/nct06834672/"},{"id":"nct06619236","kind":"trial","name":"Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer","route":"/trials/nct06619236/"},{"id":"nct07214779","kind":"trial","name":"Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression","route":"/trials/nct07214779/"},{"id":"nct07109414","kind":"trial","name":"Trial of NP-G2-044 (Prilukae) Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (ULTIMUS-1)","route":"/trials/nct07109414/"}],"idea":[{"id":"idea-fra-adc-sequencing-ovarian","kind":"idea","name":"Sequence folate-receptor ADCs by payload class","route":"/ideas/idea-fra-adc-sequencing-ovarian/"}],"target":[{"id":"folr1","kind":"target","name":"Folate receptor alpha","route":"/targets/folr1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"cancer":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"}]}}