Combination Approaches With ADCs and Emerging Clinical Strategies in Breast Cancer

This section reviews the scientific and clinical rationale for combination therapy involving ADCs. Dr Tarantino introduces the concept by noting the rapid expansion of ADC trials and the increasing interest in pairing these agents with targeted therapies and immunotherapy. Dr Mouabbi explains that combination strategies may further enhance the activity of ADCs and produce deeper and more durable responses.

The speakers discuss why datopotamab deruxtecan is well positioned to support combination therapy. They highlight that this agent produces minimal neutropenia, which allows for safer integration with treatments that cause bone marrow suppression such as CDK4 and CDK6 inhibitors. Dr Mouabbi explains that a favorable hematologic profile improves feasibility for combination approaches without excessive toxicity.

The discussion expands to the role of immunotherapy. The experts describe how ADC mediated tumor cell death can stimulate antigen presentation and immune activation. This provides a biologic basis for combining ADCs with checkpoint inhibitors. They note that early studies in other tumor types, including urothelial cancer, have already shown encouraging activity with ADC plus immunotherapy combinations.

They then address emerging data on dual ADC combinations that target complementary pathways. Although dual ADC therapy is not yet ready for routine clinical use in breast cancer, the speakers emphasize the potential for high response rates when payloads and targets are carefully selected.

The section closes by highlighting the importance of ongoing research. The experts encourage clinicians to follow combination trials closely because these studies may define the next generation of treatment standards. They emphasize that thoughtful design, toxicity monitoring, and patient selection will be central to safely integrating combination therapy into practice.