For endometrial or cervical cancer patients who progress after receiving a checkpoint inhibitor, re-challenging with a single-agent immunotherapy is a less desirable approach. Emerging data suggests that a combination therapy—such as an ICI paired with a TKI like lenvatinib or a bispecific antibody—offers a more promising chance of response.
Despite significant interest, circulating tumor DNA (ctDNA) is not yet an actionable tool for guiding the duration of maintenance immunotherapy in endometrial cancer. While studies like DuoE show ctDNA levels correlate with outcomes, there is no evidence to support using its clearance to decide when to stop treatment. It remains a prognostic, not a predictive, biomarker for this purpose.
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.
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.
While checkpoint inhibitors are standard for dMMR endometrial cancer, a clear clinical boundary is emerging for the pMMR subgroup. Based on trial data showing no benefit for fully resected disease (e.g., B21 trial), oncologists are not offering immunotherapy to pMMR patients without measurable disease, avoiding significant toxicity without proven efficacy.
The future of GYN oncology immunotherapy is diverging. For responsive cancers like endometrial, the focus is on refining biomarkers and overcoming resistance. For historically resistant cancers like ovarian, the strategy shifts to using combinatorial approaches (e.g., CAR-NKs, vaccines) to fundamentally alter the tumor microenvironment itself, making it more receptive to an immune response.