The glucocorticoid receptor antagonist relacorilant does not require biomarker testing for patient selection. Its target is ubiquitously expressed in over 95% of ovarian cancer tissues, making it a broadly applicable therapy without the need for additional screening.
When an HRD test is inconclusive due to insufficient tumor tissue after neoadjuvant chemotherapy, it can paradoxically indicate a very strong response to treatment and high platinum sensitivity, as there is little to no residual tumor to analyze.
Given that access to ophthalmologists can be a significant bottleneck for patients, it is acceptable and practical for routine monitoring of mirvetuximab-related ocular side effects to be managed by optometrists. This pragmatic approach improves accessibility while ensuring patient safety.
The positive outcome of the KEYNOTE-B96 trial in platinum-resistant ovarian cancer, in contrast to prior failed immunotherapy trials, is likely attributable to the weekly paclitaxel backbone. This metronomic dosing promotes an immune-active tumor microenvironment, enhancing the efficacy of pembrolizumab.
When managing ocular toxicity from the ADC mirvetuximab, clinicians advocate for delaying the subsequent dose to allow the cornea to heal naturally. This approach is often preferred over an immediate dose reduction, which might unnecessarily compromise the treatment's efficacy.
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.
While retreating with a PARP inhibitor after a long progression-free interval is a viable strategy for patients with BRCA mutations, experts express caution and hesitancy in applying the same approach to patients who are HRD-deficient but BRCA wild-type, partly due to changing FDA labels.
A high-level discussion among experts reveals a growing debate about the long-term use of antibody-drug conjugates (ADCs). They question whether the benefits of continuous chemotherapy delivery outweigh the cumulative and novel toxicities, suggesting a need for a more balanced approach to treatment duration.
Emerging antibody-drug conjugates (ADCs) targeting folate receptor alpha, such as Sofiem and T-SAM, are demonstrating strong response rates in ovarian cancer patients with both high and low FRα expression, challenging the current high-expression requirement for approved ADCs like mirvetuximab.
While the risk of secondary leukemia (MDS/AML) from PARP inhibitors is low (0.5-1.5%) in the frontline setting, it escalates dramatically to 8-11% in heavily pretreated patients or those receiving therapy for more than two years, highlighting a significant long-term safety concern.