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.

The confirmatory Code Break 200 study for sotorasib demonstrated a statistically significant improvement in progression-free survival (PFS) over docetaxel. However, it failed to show a similar benefit in overall survival (OS), a critical distinction for oncologists weighing long-term patient outcomes.

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.

Real-world data shows that in platinum-sensitive ovarian cancer patients who have progressed on PARP inhibitors, subsequent platinum-based chemotherapy has a surprisingly low response rate of only 20%. This quantifies a significant opportunity for highly active ADCs to potentially replace platinum in this growing patient population.

Similar to findings in small cell lung cancer, immunotherapy combinations in advanced ovarian cancer may create a "tail on the curve." Even if median survival benefit is modest, data shows the survival curves remain separated long-term, suggesting a small but significant subset of patients achieves durable survival of 3-5 years.

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.

After a decade with no new therapies improving survival, the landscape for platinum-resistant ovarian cancer is transforming. The recent successes of mirvetuximab, the pembrolizumab/paclitaxel combo, and relacorilant/nab-paclitaxel have all demonstrated statistically significant overall survival benefits, heralding a new era of effective options.

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.

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.