# Caution: TOP1 ADC immediately after TOP1 ADC

Source: https://onco.cc/pairings/adc-after-adc-caution/  
OnCo record `adc-after-adc-caution` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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

## Summary

This caution pairing concerns giving a second antibody-drug conjugate with a topoisomerase 1 payload straight after a first, for example Sacituzumab govitecan after Trastuzumab deruxtecan, in Triple-negative breast cancer (TNBC) and HR-positive / HER2-negative breast cancer. Payload resistance (SLFN11 loss, TOP1 mutations, ABCG2 efflux) is shared across TOP1 ADCs regardless of antigen, so switching antigen does not overcome it. Retrospective series, including SATEEN and BRE-354 at ESMO Breast 2026, show shorter progression-free survival for the second TOP1 ADC, particularly back-to-back; some data suggest an intervening chemotherapy restores sensitivity. Prospective sequencing trials are ongoing; see the ADC sequencing entry and the idea of payload-class switching.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Trastuzumab deruxtecan + Sacituzumab govitecan
- Type: caution
- 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.

## Sources

- Abelman et al., Sequential use of antibody-drug conjugate after antibody-drug conjugate in metastatic breast cancer (ASCO 2023, abstract 1022): https://doi.org/10.1200/jco.2023.41.16_suppl.1022

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/), [TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET](https://onco.cc/roadmaps/trop2-adc-roadmap/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/), [Sequential multiple-assignment randomised trials to find the best order of ADCs](https://onco.cc/ideas/idea-tr2-smart-sequencing-adc/)

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