{"entity":{"id":"idea-tdxd-first-then-nothing","kind":"idea","name":"Can T-DXd alone cure early HER2-positive disease?","aka":[],"tldr":"If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.","summary":"The idea is a response-adapted trial in early HER2-positive breast cancer that gives trastuzumab deruxtecan alone before surgery and, for patients who reach a pathological complete response, drops everything else: no further chemotherapy, antibodies alone or observation only. A pathological complete response predicts near-cure, PHERGain proved imaging-adapted omission is feasible, and T-DXd's complete-response rate approaches that of the best chemotherapy regimens. DESTINY-Breast11, where neoadjuvant T-DXd was followed by THP, and DESTINY-Breast05 bracket the curative setting. The test would be a single-arm study then randomised de-escalation, with PET and ctDNA as early response markers and lung toxicity as the safety endpoint.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05113251: DESTINY-Breast11","url":"https://clinicaltrials.gov/study/NCT05113251"},{"label":"ClinicalTrials.gov NCT04622319: DESTINY-Breast05","url":"https://clinicaltrials.gov/study/NCT04622319"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","trastuzumab","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr"],"trials":["destiny-breast11","destiny-breast05","phergain"],"people":[],"bottlenecks":[],"keyPapers":["paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005","paper-hera-b31-n9831-n-engl-j-med-2005","paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant T-DXd monotherapy followed by response-adapted de-escalation (no further chemotherapy; antibodies only, or observation) achieves 3-year iDFS ≥92% in pCR patients.","rationale":"pCR after HER2-directed therapy predicts near-cure; PHERGain proved imaging-adapted omission is feasible; T-DXd's pCR rate approaches the best chemotherapy-containing regimens.","test":"Single-arm then randomised de-escalation study with ctDNA and PET as early response markers; ILD monitoring as the safety endpoint.","maturity":"early-clinical"},"route":"/ideas/idea-tdxd-first-then-nothing/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"drug":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"trial":[{"id":"destiny-breast05","kind":"trial","name":"DESTINY-Breast05","route":"/trials/destiny-breast05/"},{"id":"destiny-breast11","kind":"trial","name":"DESTINY-Breast11","route":"/trials/destiny-breast11/"},{"id":"phergain","kind":"trial","name":"PHERGain","route":"/trials/phergain/"}],"paper":[{"id":"paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011","kind":"paper","name":"Adjuvant trastuzumab in HER2-positive breast cancer","route":"/key-papers/paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011/"},{"id":"paper-hera-b31-n9831-n-engl-j-med-2005","kind":"paper","name":"Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer","route":"/key-papers/paper-hera-b31-n9831-n-engl-j-med-2005/"},{"id":"paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005","kind":"paper","name":"Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer","route":"/key-papers/paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005/"}]}}