Post-Progression Therapy, Crossover, and Interpreting Survival Endpoints

Sarah L. Sammons, MD, of the University of Maryland Greenebaum Comprehensive Cancer Center, and Seth A. Wander, MD, PhD, of Massachusetts General Hospital, join Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute, to debate how post-progression therapy shapes survival interpretation in hormone receptor positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Dr Sammons calls evaluation of subsequent therapies essential, citing two similar frontline TROP2 antibody-drug conjugate trials in triple-negative disease in which crossover and post-progression imbalances tracked with divergent overall survival results, while arguing that universal crossover is not feasible given heterogeneous populations. Dr Wander says progression-free survival 2, the time to progression on next-line therapy, is only interpretable alongside crossover patterns, referencing the SONIA discussion around cyclin-dependent kinase 4/6 inhibitors, and favors time to subsequent chemotherapy and patient-reported outcomes as concrete measures, emphasizing quality of life alongside length of life in a disease not yet curable.