The treatment landscape for platinum-resistant ovarian cancer has rapidly evolved into a biomarker-driven paradigm. Clinicians must now test for and choose between therapies targeting distinct markers like folate receptor alpha (mirvetuximab), HER2 (T-DXd), and PD-L1 (pembrolizumab), requiring a sophisticated sequencing strategy.

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 novel drug relacorilant overcomes taxane resistance in ovarian cancer by targeting glucocorticoid receptors. It blocks stress-induced steroid signaling that promotes anti-apoptotic proteins, effectively re-sensitizing tumors to chemotherapy. This represents a completely new mechanism of action for this patient population.

Unlike early ADCs requiring high biomarker expression (e.g., mirvetuximab), next-generation agents show efficacy even in low-expressing tumors. This allows for broader, "all-comer" clinical trial inclusion criteria instead of biomarker-gated entry, potentially expanding patient access to these novel therapies.

The B96 trial's positive outcome in historically immunotherapy-resistant ovarian cancer is not just about adding pembrolizumab. The regimen's success is attributed to the thoughtful use of continuous weekly paclitaxel, a form of metronomic chemotherapy known to have favorable immunogenic effects, which was a deliberate, science-backed choice.

The ADC mirvetuximab is the first drug to demonstrate an overall survival benefit for platinum-resistant ovarian cancer. This groundbreaking result establishes a higher efficacy standard that subsequent therapies will likely need to meet for regulatory approval and clinical adoption, raising the bar for future drug development.

Despite the KEYNOTE-B96 trial showing a statistically significant survival benefit, the expert's enthusiasm for adding pembrolizumab in platinum-resistant ovarian cancer is only "neutral." This hesitation stems from challenges in sequencing it with other effective therapies and uncertainty about which patient subgroups truly benefit.

A new wave of antibody-drug conjugates (ADCs) is transforming ovarian cancer treatment. These 'heat-seeking missiles' deliver potent chemotherapy payloads directly to tumor cells, achieving response rates from 23% to over 60% in biomarker-selected populations. This far surpasses the efficacy of conventional chemotherapy in resistant settings.

The success of the KEYNOTE-B96 trial highlights weekly paclitaxel as a uniquely effective partner for immunotherapy in platinum-resistant ovarian cancer. Its metronomic dosing modulates the tumor microenvironment, enhances immunogenicity, and reduces immunosuppression, making it superior to other chemotherapies in this combination.