A New Era of Treatment Sequencing in Platinum-Resistant Ovarian Cancer: Integrating Immunotherapy, Antibody–Drug Conjugates, and Targeted Therapies

Platinum-resistant ovarian cancer (PROC) has historically been treated with sequential non-platinum chemotherapy, with bevacizumab added when appropriate. The therapeutic landscape has expanded with positive randomized phase III data for pembrolizumab plus weekly paclitaxel with or without bevacizumab (KEYNOTE-B96), mirvetuximab soravtansine (MIRV) in FRα-high disease (MIRASOL), and relacorilant plus nab-paclitaxel (ROSELLA). Trastuzumab deruxtecan (T-DXd) has also shown substantial activity in previously treated HER2-expressing ovarian cancer, although its ovarian cohort was small, nonrandomized, and not restricted to PROC. These trials enrolled different populations and do not establish a cross-trial efficacy hierarchy. We therefore review the development of immunotherapy leading to KEYNOTE-B96, compare newer strategies with established PROC treatments, distinguish phase III evidence from regulatory approval and routine availability, and propose an evidence-informed framework for treatment selection and sequencing. The framework prioritizes current treatment opportunity while accounting for biomarker eligibility, prior treatment, residual toxicity, treatment and financial burden, patient priorities, and the feasibility of later-line therapy.