trastuzumab-deruxtecan

Overview

Trastuzumab deruxtecan (T-DXd) is an anti-HER2 antibody-drug conjugate (ADC) composed of trastuzumab linked to a topoisomerase I inhibitor payload. It has FDA approvals in HER2-positive and HER2-low breast cancer, HER2-positive gastric/gastroesophageal junction adenocarcinoma, HER2-mutant NSCLC, and other HER2-expressing solid tumors.

Evidence in the corpus

  • In 177 cervical cancers profiled by MSK-IMPACT, trastuzumab deruxtecan is under investigation (NCT04482309) for HER2-mutant/amplified cervical cancer; ERBB2 is altered in 28% of unusual endocervical adenocarcinoma (UEA) and 12% overall, establishing ERBB2 as a likely important target PMID:37643132.
  • In endometrial carcinoma, ERBB2 amplification enriched in Black patients (12% vs 3% in White patients) represents a therapeutic opportunity with trastuzumab deruxtecan; activity was noted even in low-HER2-expressing carcinosarcomas PMID:37651310.
  • In metastatic urothelial carcinoma (mUC), ERBB2 alterations (detected in 14% of cfDNA samples from the CALGB 90601 cohort) were independently associated with shorter OS (multivariable HR 1.64, 95% CI 1.08–2.49; p=0.019). The authors highlight trastuzumab deruxtecan as a candidate HER2-directed antibody-drug conjugate for ERBB2-altered mUC, citing response rates of 33–83% in this setting. PMID:40256659
  • HER2-positive CCA: basket phase II across 7 cohorts ORR 37.1% overall, 22.0% in 41 CCA patients; mPFS 4.6 mo, mOS 7.0 mo in CCA; risk of interstitial pneumonitis noted PMID:25526346

Resistance mechanisms

  • Not directly characterized in the corpus.

Cancer types (linked)

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25526346

This page was processed by crosslinker on 2026-05-14.