ESMO Spotlight: Flagship ADCs move into early-stage cancer to validate chemo-displacement ambitions

Next-generation antibody-drug conjugates (ADCs) are showing unprecedented efficacy in early-stage cancer, aiming to displace chemotherapy as standard care in multiple solid tumors3 4 7 13.

Pivotal phase 3 trials DESTINY-Breast05 and DESTINY-Breast11 presented at ESMO 2025 demonstrate that trastuzumab deruxtecan (ENHERTU) significantly improves outcomes in early-stage HER2-positive breast cancer, highlighting its potential as a foundational curative-intent therapy4 7 9.

For the first time, datopotamab deruxtecan (DATROWAY) has been shown in the TROPION-Breast02 trial to significantly improve overall survival versus chemotherapy in first-line metastatic triple-negative breast cancer for patients ineligible for immunotherapy. This marks the first survival benefit of an ADC over chemotherapy in this population4 11.

AstraZeneca and Daiichi Sankyo's internal ADC pipelines are rapidly advancing, with candidates like AZD5335 (targeting folate receptor α in ovarian cancer) showing efficacy in early human trials and a broader ambition to develop ADC-based therapies across tumor types2 4.

The movement of ADCs into earlier lines of therapy is reshaping treatment paradigms by aiming to reduce recurrence risk and ultimately replace or reduce the need for traditional chemotherapy3 4 7 13.

New data highlight the necessity for precision:
careful toxicity management (e.g., interstitial lung disease risks with T-DXd) and development of improved predictive biomarkers, such as quantitative proteomic and transcriptomic assays, for optimally selecting patients for ADC therapy13.

The 2025 ESMO Congress marks a formal transition of ADCs from late-line and metastatic indications to the curative arena, affecting practice guidelines and signaling a major shift in oncology standards7 13.