How ADCs are Replacing Chemotherapy as Breast Cancer Treatment

Antibody-drug conjugates (ADCs) have emerged as a viable treatment option in various disease states in recent years. At the 16th Annual World ADC Summit in San Diego, CA, experts congregated to discuss the most prominent ADC news.

During the Summit, Aditya Bardia, MD, MPH, FASCO, delivered a presentation titled “Reviewing the ADC Clinical & Approval Landscape: What Direction are ADCs Heading to Reshape Frontline Oncology Treatments For Patients?”. In this presentation, he discussed data from top trials and highlighted significant details pertaining to the efficacy and safety of the agents.

In various breast cancer types, Bardia stated that ADCs are slowly replacing preferred regimens. In HER2-positive breast cancer and metastatic triple-negative breast cancer, for example, ADCs are becoming favorable vs chemotherapy.

Additionally, Bardia highlighted top trials in this space as being the phase 3 ASCENT-05 trial (NCT05633654), evaluating sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) vs treatment of physician’s choice in patients with triple-negative breast cancer post-surgery and pre-clinical treatment, the phase 3 TROPION-Breast03 trial (NCT05629585), evaluating datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) with or without durvalumab (Imfinzi) in triple-negative breast cancer with residual invasive disease at surgical resection after neoadjuvant therapy, and the phase 3 TROPION-Breast04 trial (NCT06112379), evaluating Dato-DXd plus durvalumab as neoadjuvant and adjuvant treatment for triple-negative or hormone receptor (HR)–low/HER2-negative breast cancer.

Bardia is a professor in the department of medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the University of California Los Angeles Health Jonsson Comprehensive Cancer Center.

Transcript:

ADCs are slowly replacing chemotherapy. For HER2-positive metastatic breast cancer, we’ve seen that trastuzumab deruxtecan is superior vs a chemotherapy-based backbone in combination with trastuzumab [Herceptin] and pertuzumab [Perjeta; THB]. The phase 3 DESTINY-Breast09 study [NCT04784715] showed that T-DXd was clearly superior to the THB regimen. Similarly, in first-line metastatic triple-negative breast cancer, we’ve seen that ADCs are better than chemotherapy. For HR–positive breast cancer, after endocrine-based therapies have been exhausted, ADCs are superior to chemotherapy. ADCs are slowly replacing chemotherapy in the metastatic setting. In the future, they likely will replace chemotherapy in the localized breast cancer setting as well.

The pivotal studies to look out for in the future are ASCENT-05, along with TROPION-Breast03, because they would be looking at TROP2 ADCs in the adjuvant setting in patients who have residual disease despite neoadjuvant therapy. TROPION-Breast04 would be looking at neoadjuvant Dato-DXd. These are pivotal studies in the triple-negative breast cancer space, which could potentially change how we treat triple-negative breast cancer.

Reference

Bardia A. Moving forward with ADCs in clinic: challenges and opportunities. Presented at the 2025 World Antibody Drug Conjugate Conference; San Diego, CA; November 3-6, 2025.