Treatment Sequencing in Platinum-Resistant Epithelial Ovarian Cancer After MIRASOL, KEYNOTE-B96, and ROSELLA.

Area of Science:

• Oncology
• Gynecologic Oncology
• Translational Medicine

Background:

• Platinum-resistant epithelial ovarian cancer (EOC) management has historically lacked therapeutic differentiation, relying on non-platinum chemotherapy with limited efficacy.
• Previous approaches, including bevacizumab, failed to overcome short progression-free survival, poor response durability, cumulative toxicity, and lack of biological selection.
• Recent Phase III trials (MIRASOL, KEYNOTE-B96, ROSELLA) have introduced novel therapeutic strategies and biomarkers for platinum-resistant EOC.

Purpose of the Study:

• To review and clarify how recent Phase III trial evidence should inform treatment allocation and sequencing in platinum-resistant EOC.
• To define the distinct evidence anchors provided by new therapeutic modalities and their selection criteria.
• To outline a framework for rational, patient-specific treatment sequencing integrating biomarker status and clinical factors.

Main Methods:

• Review of Phase III trial data from MIRASOL (mirvetuximab soravtansine), KEYNOTE-B96 (pembrolizumab + paclitaxel), and ROSELLA (relacorilant + nab-paclitaxel).
• Analysis of established biomarkers: folate receptor alpha (FRα) and programmed death ligand 1 (PD-L1) combined positive score (CPS).
• Evaluation of tumor-biomarker-independent approaches and integration of clinical factors for treatment sequencing.

Main Results:

• MIRASOL established mirvetuximab soravtansine (FRα-targeted ADC) for FRα-positive platinum-resistant EOC.
• KEYNOTE-B96 demonstrated improved outcomes with pembrolizumab plus paclitaxel (± bevacizumab) in PD-L1 CPS-positive platinum-resistant EOC.
• ROSELLA showed enhanced activity of relacorilant (GR antagonist) with nab-paclitaxel, selected by clinical criteria.

Conclusions:

• Three distinct evidence anchors exist: FRα-targeted ADC, PD-L1 CPS-selected chemoimmunotherapy, and biomarker-independent GR antagonism.
• These options do not form a simple hierarchy; treatment sequencing requires careful consideration of biomarker eligibility, prior therapies, toxicity profiles, and patient priorities.
• The central challenge is developing patient-specific sequencing strategies that integrate both biomarker-directed and biomarker-independent treatment options.