Advances in Platinum-Resistant Ovarian Cancer: Comparing Relacorilant and Other Treatments

✨ Why Is This Article Needed?

Platinum-based chemotherapy is the cornerstone of first-line treatment for advanced ovarian cancer. Unfortunately, approximately 70% of patients with ovarian cancer are diagnosed at stage 3 or 4. The late onset of symptoms, lack of an approved screening method and biologically resistant nature of ovarian cancer increase the likelihood of recurrence, even after an initial response to treatment.

However, options become even more limited when the disease develops resistance to this treatment. In this patient group, described as "platinum-resistant," response rates are low and expected overall survival is shorter.

As of 2025, both conventional and new targeted treatments promise striking changes in this field. This article compares all current options, especially the findings presented at ASCO 2025 and simultaneously reported in THE LANCET from the ROSELLA study, which highlighted the relacorilant + nab-paclitaxel combination.

🔎 4 Key Facts About Platinum-Resistant Ovarian Cancer

• 🧬 Definition: Ovarian cancer that, after a response to platinum-based chemotherapy, recurs within 6 months is defined as "platinum-resistant."

• 📉 High Risk of Recurrence: Among patients diagnosed at an advanced stage, approximately 70% experience recurrence within the first year , and most of these recurrences are platinum-resistant.

• ⏳ Limited Effectiveness: With standard treatments used for platinum-resistant disease, median progression-free survival < 6 months has been reported.

• 🔬 Treatment Approaches Are Expanding: New targeted agents (e.g., relacorilant, Elahere®) and biomarker-based strategies have begun to yield promising results in this challenging patient population.

🧪 1. Phase 3 ROSELLA: Is Relacorilant Bringing a New Standard?

Relacorilantis an experimental oral drug that selectively blocks glucocorticoid receptors (GR). The ROSELLA study was designed to investigate whether adding relacorilant to standard chemotherapy improves progression-free and overall survival in platinum-resistant ovarian cancer.

In platinum-resistant tumors, the cortisol-mediated cellular stress response may increase resistance to chemotherapy. Relacorilant suppresses this cortisol signal, making tumor cells more sensitive to chemotherapy. It therefore showed the potential to improve response rates and survival, particularly when used with nab-paclitaxel.

Patient Profile: 381 patients with platinum-resistant epithelial ovarian, fallopian tube or peritoneal cancer who had received 1-3 prior lines of therapy; patients previously treated with bevacizumab were included.

Design: An open-label, phase 3 randomized controlled trial at 117 centers in 14 countries.

Arms:

• Relacorilant (150 mg orally) + nab-paclitaxel (80 mg/m², days 1-8-15)

• Nab-paclitaxel monotherapy (100 mg/m²)

Main Findings:

• Median progression-free survival (mPFS): 6.54 vs 5.52 months | HR: 0.70 (p = 0.0076)

• Median overall survival (mOS): 15.97 vs 11.50 months | HR: 0.69 (p = 0.0121)

• Objective response rate (ORR): 36.9% vs 30.1% | Clinical benefit rate: 51.1% vs 38.9% (p = 0.016)

Safety Profile:

• Neutropenia (Grade ≥3): 44% vs 25%

• Anemia (Grade ≥3): 18% vs 8%

• Fatigue (Grade ≥3): 9% vs 2%

• Ascites rate: 5% vs 11%

• No treatment-related deaths were observed.

✅ 2. Approved Standard Treatments

Bevacizumab + Chemotherapy (AURELIA)

• FDA Approval: 2014

• Combinations: PLD, topotecan, paclitaxel

• PFS: 6.7 vs 3.4 months | ORR: 27% vs 12%

Mirvetuximab Soravtansine (Elahere®)

• FDA Approval: 2022 (accelerated), 2024 (full approval)

• Indication: FRα+ platinum-resistant patients who have received 1-3 prior lines of therapy

• ORR: 42% vs 16% | OS: 16.5 vs 12.7 months | PFS: 5.6 vs 4.0 months

Pegylated Liposomal Doxorubicin (PLD), Topotecan, Gemcitabine

• Used alone or in combination with bevacizumab.

PARP Inhibitors

• Rucaparib: In BRCA-mutated, platinum-resistant patients

• Olaparib + Bevacizumab: Approved in HRD+ patients, but only when the disease is platinum- sensitive .

🔬 3. Newly Approved Targeted Treatments

Avutometinib + Defactinib (Avumpki + Fakzynja®)

• FDA Approval: 2025

• Indication: KRAS-mutated, recurrent low-grade serous ovarian cancer (LGSOC)

• ORR: 44% (RAMP 201)

Mechanism: The MEK inhibitor avutometinib and FAK inhibitor defactinib act synergistically to target KRAS-mutated cells.

🏥 4. Locoregional Treatment Methods

Secondary Cytoreductive Surgery (GOG-0213)

• OS: 50.6 vs 64.7 months, but statistical significance was not reached (HR: 1.72, p = 0.08)

• Limitation: May be recommended only for selected patients in whom complete resection can be achieved

HIPEC (Heated Intraperitoneal Chemotherapy)

a. Phase 3 CHIPOR – With Cisplatin

• OS: 54.3 vs 45.8 months | HR: 0.73 | p = 0.024 (first platinum-sensitive recurrence)

b. Taipei 2024 – With Oxaliplatin

• Patients: Including platinum-resistant patients

• PFS: 20.4 months | OS: 26.7 months

• Advantage: 9% renal toxicity (no Grade ≥3)

📊 Comparison Table: Current Options in Platinum-Resistant Ovarian Cancer

🔄 Conclusion and Clinical Perspective

In the treatment of platinum-resistant ovarian cancer, biomarker-based targeted agents, new combinations and locoregional strategies are now coming to the fore alongside conventional chemotherapy. With the ROSELLA study, the relacorilant combination emerged as a promising candidate for this challenging patient population.

✨ Multidisciplinary team assessment, molecular profiling and keeping up with the latest scientific developments are critical to success in clinical practice.