While antibody-drug conjugates (ADCs) are an exciting frontier in endometrial cancer, a critical challenge is emerging: determining optimal duration for maintenance therapies. Experts are concerned about committing patients to long-term, potentially toxic treatments without clear stopping rules, a key question for future trials.

In patients achieving a complete response on EV-pembrolizumab, leading oncologists are using circulating tumor DNA (ctDNA) clearance in clinical practice to increase confidence and facilitate shared decision-making around stopping treatment, despite it not being standard of care.

While not yet validated, ctDNA is being used by clinical experts as a de-escalation tool to provide confidence when stopping long-term maintenance therapies like PARP inhibitors. This novel application focuses on reducing treatment burden rather than solely detecting disease progression.

Experts predict that emerging cell-free DNA (ctDNA) tests for lymphoma will shift treatment from fixed durations to a response-adapted approach. Monitoring minimal residual disease via ctDNA will allow clinicians to tailor the length of therapy based on the quality of response.

In the Serena 6 trial, patients whose circulating tumor DNA (ctDNA) was cleared after switching to camazestrant had a significantly improved overall survival (HR 0.4). This exploratory finding suggests ctDNA monitoring can be a potent early indicator of long-term treatment success, potentially reshaping how therapeutic efficacy is measured long before imaging can.

Measuring circulating tumor DNA (ctDNA) to detect minimal residual disease (MRD) after treatment is a powerful predictor of recurrence. This biomarker could be used as a surrogate endpoint in clinical trials, allowing for accelerated drug approvals based on early data rather than waiting years for survival outcomes.

Despite acknowledging that a one-size-fits-all treatment duration is suboptimal, the expert consensus is to follow the study protocol. This conservative, evidence-based approach prevails due to the absence of validated biomarkers, like ctDNA, to safely guide treatment de-escalation for individual patients.

As multiple effective Antibody-Drug Conjugates (ADCs) become available, the primary clinical challenge is no longer *if* they work, but *how* to use them best. Key unanswered questions involve optimal sequencing, dosing for treatment versus maintenance, and overall length of therapy, mirroring issues already seen in breast cancer.

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.