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When Enhertu stops working, the next ADC should probably carry a different kind of payload, such as the tubulin inhibitors in Kadcyla or ARX788, rather than another topoisomerase drug.
The idea is to choose the next HER2 antibody-drug conjugate after trastuzumab deruxtecan by payload class: a tubulin-inhibitor ADC such as trastuzumab emtansine, ARX788 or disitamab vedotin rather than another topoisomerase 1 payload. T-DXd is now used first line and in early disease, so most later HER2 ADC use will follow it; resistance often spares HER2 expression but involves TOP1 or SLFN11 changes, and TOP1 payloads show cross-resistance. The hypothesis is that a tubulin-payload ADC gives a higher response rate and longer progression-free survival than a second TOP1-payload ADC when HER2 is retained. The test is a randomised phase 2 stratified by HER2 immunohistochemistry on a progression biopsy, measuring SLFN11 and TOP1; the evidence is preclinical.
One of the most cited trial reports Europe PMC returns for Trastuzumab deruxtecan in HER2-positive breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.
This is the paper Europe PMC returns for registry id NCT02131064 with the most citations, so it is the natural first reading for anyone following the KRISTINE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Shares Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial, Trastuzumab emtansine, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
Shares ARX788, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
Shares Trastuzumab emtansine, Trastuzumab deruxtecan, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
Shares KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment, Trastuzumab deruxtecan, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
Shares Sequential multiple-assignment randomised trials to find the best order of ADCs, ADC sequencing, Trastuzumab deruxtecan.
Shares ARX788, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
Shares KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment, Trastuzumab emtansine, HER2-positive breast cancer.
Shares Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer, Trastuzumab deruxtecan, HER2-positive breast cancer.