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Caution: TOP1 ADC immediately after TOP1 ADC

Giving a second ADC with the same kind of payload straight after the first often does not work well.

Retrospective series (ESMO Breast 2026 SATEEN/BRE-354 and others) show shorter PFS for the second TOP1-payload ADC, particularly when given back-to-back. Some data suggest an intervening chemotherapy restores sensitivity. Prospective sequencing trials are ongoing.

Rationale
Payload resistance (SLFN11 loss, TOP1 mutations, ABCG2 efflux) is shared across TOP1 ADCs regardless of antigen; antigen switching does not overcome it.
Evidence
Retrospective; prospective trials pending.

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