After numerous failed trials suggested immunotherapy was ineffective in ovarian cancer, the KEYNOTE B96 study marks a turning point. Combining pembrolizumab with chemotherapy showed statistically significant improvements in both progression-free and overall survival in platinum-resistant patients, reviving the entire therapeutic class for this disease.
The clinical lexicon for recurrent ovarian cancer is evolving. The term "platinum resistant" is being replaced by "platinum ineligible." This reflects a more nuanced clinical judgment that platinum-based chemotherapy is not the best option for a patient's recurrence, rather than being based solely on a time-defined interval of relapse.
A key challenge is treating ovarian cancer that progresses on PARP inhibitors. A subgroup analysis of the REJOYCE study found that the cadherin-6-directed ADC, Ralodotatug deruxtecan (RDXD), had a high response rate of 58% in this specific, difficult-to-treat population, positioning it as a potential future therapy for this clinical scenario.
A "tsunami" of antibody-drug conjugates (ADCs) are in development for ovarian cancer, but many share the same TOP1 inhibitor payload. This creates a significant future clinical challenge: after a patient progresses on one such ADC, it is unknown if another with the same payload will be effective, creating an urgent need for sequencing data.