B7-H4 ADCs: Key Questions for Clinical Integration

B7-H4–targeted antibody-drug conjugates (ADCs) are an emerging area of investigation in gynecologic cancers, with data presented at the 2026 European Society for Medical Oncology (ESMO) Congress, including findings from the BEHOLD-1 trial (NCT06431594). As development advances, questions surrounding biomarker testing, toxicity management, and treatment sequencing will influence how these agents are incorporated into clinical practice.

At the ESMO Congress, Shannon Westin, MD, MPH, FASCO, FACOG, professor in the department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, sat down with Targeted Oncology to discuss practical considerations for integrating B7-H4–directed therapies into treatment strategies. If these agents receive biomarker-based approvals, B7-H4 testing may become another component of routine molecular profiling, building on established testing practices in ovarian and other gynecologic cancers.

Westin also highlights the importance of evaluating tolerability and treatment duration, particularly if ADCs are used in the maintenance setting. Although clinicians may accept a different toxicity burden in later-line treatment, prolonged exposure during maintenance raises questions about quality of life, treatment adherence, and the duration of therapy. Trial designs will need to clarify whether treatment should continue for a defined period or until disease progression.

Treatment sequencing presents another challenge as ADCs move into earlier lines of therapy. Westin discusses uncertainty surrounding the reuse of ADCs and whether resistance to a shared cytotoxic payload could limit the activity of a subsequent agent, even when it targets a different antigen. Changes in target expression may also affect responses to sequential ADCs directed at the same receptor.

As the ADC landscape expands, Westin emphasizes the need for additional payloads and alternative targeted therapies to provide options beyond successive ADC regimens. These considerations will be important as clinicians determine how to sequence emerging agents while balancing treatment efficacy, toxicity, and patients’ quality of life.