# Platinum-resistant ovarian cancer

Source: https://onco.cc/cancers/platinum-resistant-ovarian-cancer/  
OnCo record `platinum-resistant-ovarian-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Platinum-resistant recurrent ovarian cancer; Platinum-refractory ovarian cancer; Platinum-free interval under six months; PROC
- Tags: subtype-page
- 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

## Standard of care

- Folate receptor alpha-high: Mirvetuximab soravtansine with ophthalmic monitoring (MIRASOL). ([Mirvetuximab soravtansine](https://onco.cc/drugs/mirvetuximab-soravtansine/), [MIRASOL / GOG-3045](https://onco.cc/trials/mirasol/), [Folate receptor alpha](https://onco.cc/targets/folr1/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/))
- PD-L1 CPS 1 or more: Pembrolizumab with weekly paclitaxel, with bevacizumab where not previously given (KEYNOTE-B96). ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [KEYNOTE-B96 / ENGOT-ov65](https://onco.cc/trials/keynote-b96/), [PD-L1](https://onco.cc/targets/pdl1/))
- Any expression status: Relacorilant with nab-paclitaxel (ROSELLA); or single-agent weekly paclitaxel, pegylated liposomal doxorubicin, topotecan or gemcitabine with bevacizumab if bevacizumab-naive (AURELIA). ([Relacorilant](https://onco.cc/drugs/relacorilant/), [ROSELLA / GOG-3073](https://onco.cc/trials/rosella/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pegylated liposomal doxorubicin](https://onco.cc/drugs/pegylated-liposomal-doxorubicin/), [Topotecan](https://onco.cc/drugs/topotecan/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/))
- Later lines: Clinical trials of antibody-drug conjugates against CDH6, folate receptor alpha, B7-H4 and TROP2; hormonal therapy in receptor-positive low-grade disease. ([Raludotatug deruxtecan](https://onco.cc/drugs/raludotatug-deruxtecan/), [REJOICE-Ovarian01](https://onco.cc/trials/rejoice-ovarian01/), [Rinatabart sesutecan](https://onco.cc/drugs/rinatabart-sesutecan/), [RAINFOL-01 (Rina-S)](https://onco.cc/trials/rainfol-01/), [Luveltamab tazevibulin](https://onco.cc/drugs/luveltamab-tazevibulin/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/))
- Supportive care: Early palliative care, drainage of ascites, management of bowel obstruction and nutritional support alongside anticancer treatment. ([Ovarian cancer](https://onco.cc/cancers/ovarian/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ovarian_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Ovarian_cancer

## Connected records

- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Luveltamab tazevibulin](https://onco.cc/drugs/luveltamab-tazevibulin/), [Mirvetuximab soravtansine](https://onco.cc/drugs/mirvetuximab-soravtansine/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pegylated liposomal doxorubicin](https://onco.cc/drugs/pegylated-liposomal-doxorubicin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Raludotatug deruxtecan](https://onco.cc/drugs/raludotatug-deruxtecan/), [Relacorilant](https://onco.cc/drugs/relacorilant/), [Rinatabart sesutecan](https://onco.cc/drugs/rinatabart-sesutecan/), [Topotecan](https://onco.cc/drugs/topotecan/)
- trials: [A Phase 2, Open-label, Single-arm Study Of Autologous M-CENK Adoptive Cell Therapy And N-803 (IL-15 Superagonist) In Combination With Gemcitabine In P](https://onco.cc/trials/nct06710288/), [A Study Comparing BL-B01D1 With the Investigator's Choice of Chemotherapy in Patients With Platinum-resistant Recurrent Epithelial Ovarian Cancer(PANK](https://onco.cc/trials/nct06994195/), [A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer](https://onco.cc/trials/nct05128825/), [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](https://onco.cc/trials/nct07546500/), [A Study of B013 in Combination With Paclitaxel in Patients With Platinum-resistant Recurrent Ovarian Cancer.](https://onco.cc/trials/nct06434610/), [A Study of INCB123667 in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression](https://onco.cc/trials/nct07023627/), [A Study of LBL-024 in Combination With Paclitaxel ± Bevacizumab for the Treatment of Platinum-resistant Ovarian Cancer](https://onco.cc/trials/nct07042802/), [A Study of SHR-A1811 in Subjects With Ovarian Cancer](https://onco.cc/trials/nct06828354/), [A Study to Assess Adverse Events and Change in Disease Activity in Participants With Platinum-Resistant Advanced High-Grade Epithelial Ovarian, Primar](https://onco.cc/trials/nct06682988/), [A Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer (BEHOLD-Ovarian01)](https://onco.cc/trials/nct07286266/), [An Extension Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Can](https://onco.cc/trials/nct07604766/), [AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer](https://onco.cc/trials/nct07218809/), [Cancer Stem Cell Assay Directed Chemotherapy in Recurrent Platinum Resistant Ovarian Cancer](https://onco.cc/trials/nct03949283/), [CATALINA-2: A Clinical Study of TORL-1-23 in Platinum-resistant Ovarian Cancer.](https://onco.cc/trials/nct06690775/), [Chiauranib Plus Weekly Paclitaxel in Patients with Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer](https://onco.cc/trials/nct04921527/), [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)](https://onco.cc/trials/nct05281471/), [FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC](https://onco.cc/trials/nct06303505/), [HS-20089 for Injection in Patients With Platinum-Resistant Recurrent Epithelial Ovarian Cancer](https://onco.cc/trials/nct06855069/), [IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurren](https://onco.cc/trials/nct06014528/), [Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer](https://onco.cc/trials/nct06787612/), [KEYNOTE-B96 / ENGOT-ov65](https://onco.cc/trials/keynote-b96/), [MIRASOL / GOG-3045](https://onco.cc/trials/mirasol/), [ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer](https://onco.cc/trials/nct05446298/), [Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) ](https://onco.cc/trials/nct05271318/), [RAINFOL-01 (Rina-S)](https://onco.cc/trials/rainfol-01/), [REJOICE-Ovarian01](https://onco.cc/trials/rejoice-ovarian01/), [ROSELLA / GOG-3073](https://onco.cc/trials/rosella/), [SHR-A1921 for Injection in Patients With Platinum-Resistant Recurrent Epithelial Ovarian Cancer](https://onco.cc/trials/nct06394492/), [Study of IBI354 Versus Investigator's Choice of Chemotherapy in Patients With Platinum-resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer](https://onco.cc/trials/nct06834672/), [Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer](https://onco.cc/trials/nct06619236/), [Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression](https://onco.cc/trials/nct07214779/), [Trial of NP-G2-044 (Prilukae) Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (ULTIMUS-1)](https://onco.cc/trials/nct07109414/)
- ideas: [Sequence folate-receptor ADCs by payload class](https://onco.cc/ideas/idea-fra-adc-sequencing-ovarian/)
- targets: [Folate receptor alpha](https://onco.cc/targets/folr1/), [PD-L1](https://onco.cc/targets/pdl1/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- cancers: [Ovarian cancer](https://onco.cc/cancers/ovarian/)

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