Charles E Geyer MD; ESMO 2025: Antibody Drug Conjugate T-DXd Brings Longer Cancer-Free Survival for Patients with HER2-Positive Early Breast Cancer and Residual Invasive Disease

Antibody Drug Conjugate T-DXd Brings Longer Cancer-Free Survival for Patients with HER2-Positive Early Breast Cancer and Residual Invasive Disease

An interview with:

Charles E Geyer MD, Breast Medical Oncologist, University of Pittsburgh Hillman Cancer Center, Pittsburgh USA, Chief Scientific Officer, NSABP Foundation.

BERLIN, Germany— The antibody drug conjugate trastuzumab deruxtecan (T-DXd) was found to bring improved disease-free survival among patients with high-risk HER2-positive primary breast cancer who had residual invasive disease after neoadjuvant therapy, compared to a control group of patients who were treated with trastuzumab emtansine (T-DM1) after the same neoadjuvant therapy.

This was reported in an interim analysis of the DESTINY-Breast05 study at the European Society for Medical Oncology Annual Congress in Berlin by lead author Charles Geyer MD, Breast Medical Oncologist at the University of Pittsburgh Hillman Cancer Center in Pittsburgh, USA, who is also Chief Scientific Officer for the NSABP Foundation. After the conference he talked with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Charles E Geyer MD

IN: [GOODWIN]”Welcome to the Audio Journal of Oncology….

OUT: ……Oncology, I’m Peter Goodwin”  21:18secs

ESMO 2025 Abstract:

LBA1 – Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05

https://www.annalsofoncology.org/article/S0923-7534(25)04791-X/fulltext

Speakers

Charles E. Geyer (Pittsburgh, United States of America)

Authors

Charles E. Geyer (Pittsburgh, United States of America) Yeon Hee Park (Seoul, Republic of Korea) Zhi-Ming Shao (Shanghai, China) Chiun-Sheng Huang (Taipei City, Taiwan) Carlos H. Barrios (Porto Alegre, Brazil) Jame Abraham (Cleveland, United States of America) Aleix Prat (Barcelona, Spain) Naoki Niikura (Kanagawa, Japan) Michael Untch (Berlin, Germany) Seock-Ah Im (Seoul, Republic of Korea) Wei Li (Changchun, China) Huiping Li (Beijing, China) Yongsheng Wang (Jinan, China) Herui Yao (Guangzhou, China) Sung-Bae Kim (Seoul, Republic of Korea) Elton Mathias (Basking Ridge, United States of America) Yuta Sato (Shinagawa-ku, Japan) Wenjing Lu (Basking Ridge, United States of America) Hanan Abdel-Monem (Basking Ridge, United States of America) Sibylle Loibl (Neu-Isenburg, Germany)

Abstract

Background

Pts with HER2+ early BC with residual invasive disease after neoadjuvant tx are at high risk of recurrence highlighting a significant unmet need. We present interim analysis results of DESTINY-Breast05 (NCT04622319), an open-label, phase 3 trial of post-neoadjuvant T-DXd vs standard of care (SOC) T-DM1 in HER2+ early BC.

Methods

Pts with residual invasive HER2+ BC after neoadjuvant tx consisting of taxane-based chemotherapy and anti-HER2 tx and at high risk for recurrence* were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks for 14 cycles. Primary endpoint was IDFS. Key secondary endpoint was DFS; others were overall survival, distant recurrence-free interval, brain metastasis–free interval (BMFI), and safety.

Results

At data cutoff (July 2, 2025), 1635 pts were randomized to T-DXd (n = 818) or T-DM1 (n = 817). Median study duration was 29.9 months with T-DXd and 29.7 months with T-DM1. IDFS and DFS benefit with T-DXd vs T-DM1 was statistically significant (HR, 0.47 each; Table); BMFI improvement with T-DXd was clinically meaningful (HR, 0.64; 95% CI, 0.35-1.17). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 50.6% of pts with T-DXd and 51.9% of pts with T-DM1; adjudicated drug-related interstitial lung disease occurred in 9.6% (n = 2 grade 5) and 1.6% of pts (0 grade 5) and were mostly grade 1 or 2. TEAEs associated with death occurred in 0.4% (n = 3) and 0.6% (n = 5) of pts, respectively. Table: LBA1

Efficacy summary at interim analysis (data cutoff, July 2, 2025)

Efficacy          T-DXd n = 818          T-DM1 n = 817          HR (95% CI)

IDFS Patients with events, n (%)   51 (6.2)           102 (12.5)       0.47 (0.34-0.66); P † = <0.0001

DFS Patients with events, n (%)     52 (6.4)           103 (12.6)       0.47 (0.34-0.66); P † = <0.0001

DFS, disease-free survival; HR, hazard ratio; IDFS, invasive disease-free survival.*Defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0 at presentation (prior to neoadjuvant therapy) or clinical stages T1-3, N0-1, M0, with axillary node-positive disease (ypN1-3) following neoadjuvant therapy.†Stratified log rank.

Conclusions

T-DXd showed a statistically significant and clinically meaningful IDFS and DFS benefit vs T-DM1, extending its superiority to post-neoadjuvant residual disease in pts with HER2+ early BC, and representing a potential new SOC. Safety of T-DXd was generally manageable with no new safety signals.

AUDIO JOURNAL OF ONCOLOGY March 19, 2025: Charles Geyer