Sequencing Strategies After Frontline ADC Therapy

The panel addresses one of the field's most pressing practical questions: what to offer after a first-line ADC, acknowledging that no prospective data yet exist to guide the decision. Panelists review the available retrospective experience, which suggests meaningful cross-resistance when sequencing agents that share a topoisomerase I payload, with shorter time on treatment for a second such ADC. The discussion explores whether an intervening therapy between ADCs might help, noting the data remain inconclusive. Panelists describe a general approach of switching to an agent with a different mechanism of action, including cytotoxic chemotherapy, and consider the role of PARP inhibitors for patients with germline or somatic BRCA alterations given the overlap in DNA damage repair. The conversation closes on optimism about the developmental pipeline, including agents with novel payloads, different targets, and bispecific antibodies. Viewers gain a grounded understanding of current sequencing thinking and its evidence gaps.