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Patients are randomised at each decision point, not just at the start, so one trial can compare whole treatment sequences rather than single drugs.
SMART designs, standard in behavioural science, randomise patients again at progression. In metastatic breast cancer where three ADCs (T-DXd, sacituzumab, Dato-DXd) and multiple payload classes compete, a SMART would compare sequences (A then B versus B then A, payload switch versus antigen switch) with a primary endpoint of time to failure of the second line or overall survival.
Shares Registry-embedded randomisation of treatment order in routine care, Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy, ADC sequencing, Too many combinations to test.
Shares Sequencing HER2 ADCs by payload after T-DXd, Payload-class switching as the rule for ADC sequencing, ADC sequencing, Acquired resistance to every therapy.
Shares Caution: TOP1 ADC immediately after TOP1 ADC, ADC sequencing, Datopotamab deruxtecan, Too many combinations to test.
Shares Payload-class switching as the rule for ADC sequencing, Too many combinations to test, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
Shares Datopotamab deruxtecan, Sacituzumab govitecan, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
Shares Registry-embedded randomisation of treatment order in routine care, Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy, Too many combinations to test.
Shares Datopotamab deruxtecan, Too many combinations to test, Sacituzumab govitecan, Antibody-drug conjugate (ADC).
Shares Drug efflux pumps (ABC transporters), ADC sequencing, Datopotamab deruxtecan, Sacituzumab govitecan.