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The decision between new regimens in platinum-resistant ovarian cancer—relicorolant/nab-paclitaxel vs. pembrolizumab/paclitaxel—hinges on the patient's need for bevacizumab. If bevacizumab is required for symptomatic disease, the relicorolant combination is off the table.
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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 B96 trial's potential approval for platinum-resistant ovarian cancer introduces a new treatment sequencing challenge. Clinicians must decide between this immunotherapy combination and the ADC mervituximab, which has a clear biomarker (foliate receptor alpha). The lack of a reliable biomarker for the B96 regimen complicates this decision-making process for patients.
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.
Although the overall trial was negative, exploratory analysis of the AGO-OV-229 study suggested patients previously treated with Bevacizumab derived more benefit from Atezolizumab, hinting at a potential synergy worth further investigation.
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.
Beyond improving disease control, adding bevacizumab to chemotherapy in platinum-resistant ovarian cancer offers a significant quality-of-life benefit. Data from the AURELIA study showed it dramatically reduces the need for paracentesis, a procedure to drain malignant ascites (abdominal fluid) that can be detrimental for patients.
For HRD-positive ovarian cancer, a strong initial response to platinum chemotherapy may justify using a PARP inhibitor alone for maintenance. A weaker response, however, suggests adding bevacizumab for a potentially greater benefit, using clinical response as a key decision-making tool.
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.
Historically, therapies for platinum-resistant ovarian cancer were so ineffective that the order of administration was irrelevant. With the advent of multiple active ADCs, the concept of treatment sequencing and potential cross-resistance based on payloads or targets has become a critical, and entirely new, clinical consideration for this disease.
