Xichun Hu MD PhD; ESMO 2025: Antibody Drug Conjugate Trastuzumab Botidotin Outperforms Trastuzumab Emtansine in Patients with HER2-Positive Unresectable or Metastatic Breast Cancer

An interview with: Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China

BERLIN, Germany—In a head-to-head comparison of two antibody drug conjugates used to treat unresectable or metastatic breast cancer, patients treated with trastuzumab botidotin lived more than twice as long before disease progression than those in the control arm receiving trastuzumab emtansine (T-DM1). This finding was announced by Chinese researchers at the 2025 Annual Congress of the European Society of Medical Oncology.

Lead author Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China talked about the findings of his groups phase three randomized controlled study with Audio Journal of Oncology reporter Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Xichun Hu MD PhD

IN: “[GOODWIN] Peter Goodwin at ESMO ..OUT: ..of Oncology, I’m Peter Goodwin 8:30 sec

ESMO ABSTRACT LBA24

“Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study”

Speaker: Xichun Hu (Shanghai, China)

Authors:

Xichun Hu (Shanghai, China) Jian Zhang (Shanghai, China) Quchang Ouyang (Changsha, China) Qingyuan Zhang (Harbin, China) Huihui Li (Jinan, China) Xu Wang (Tianjin, China) Ying Wang (Guangzhou, China) Yongmei Yin (Nanjing, China) Shusen Wang (Guangzhou, China) Yuanting Gu (Zhengzhou, Algeria) Tao Sun (Shenyang, China) Jingfen Wang (Linyi, China) Xinhong Wu (Wuhan, China) Fanfan Li (Hefei, China) Xi Chen (Fuzhou, China) Man Li (Dalian, China) Jin Yang (Xi’an, Shaanxi Province, China) Hua Yang (Baoding, China) Xiaoping Jin (Chengdu, China) Junyou Ge (CHENGDU, China)

Lecture Time

ASTRACT

Background

Trastuzumab botidotin (A166) is a HER2-directed ADC developed using a stable, protease-cleavable valine-citrulline linker conjugated to the anti-microtubule agent Duo-5. In a phase 1 study, A166 showed promising activity in heavily pretreated patients (pts) with HER2+ breast cancer (BC). Here, we first report the results from a phase 3 study (NCT06968585).

Methods

Pts with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive A166 (4.8 mg/kg Q3W) or T-DM1 (3.6 mg/kg Q3W) until disease progression or unacceptable toxicity. The primary endpoint was PFS by BICR per RECIST v1.1.

Results

A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). As of 26 April 2025, median follow-up was 14.9 mo. Median PFS was significantly longer in A166 than in T-DM1 (11.1 mo vs 4.4 mo; HR 0.39 [95% CI 0.30-0.51], p<0.0001). PFS benefit with A166 was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36 for 1 prior line; HR 0.39 for ≥2 prior lines). ORR by BICR was 76.9% vs 53.0%, and mDOR was 12.2 mo vs 5.7 mo. Although OS data were immature, a trend toward benefit was observed in A166 (HR 0.62; 95% CI, 0.38-1.03). Grade ≥3 TEAEs occurred in 69.8% of pts in A166 and 63.7% in T-DM1. The most common grade ≥3 TEAEs (≥5%) were corneal disorder, dry eye, and vision blurred in A166, and platelet count decreased, neutrophil count decreased, hypokalemia, and GGT increased in T-DM1. Among A166-treated pts who experienced any-grade ocular AEs, instrumental activities of daily living (ADL) limitations occurred in 37 (20.3%) pts, and self-care ADL limitations in 13 (7.1%) pts; these resolved in 32 (86.5%) and 12 (92.3%) pts, respectively. TEAEs led to discontinuation in 1.1% of pts in A166 and 3.8% in T-DM1. No TEAE led to death in A166, compared with 1.1% in T-DM1.

Conclusions

A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease.

Clinical trial identification

NCT06968585.

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Funding

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Disclosure

1. Jin, J. Ge: Financial Interests, Institutional, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.

Xichun Hu MD, PhD

Medical Oncology

Xuhui, Shanghai, China

Xi-Chun Hu, M.D., Ph. D., is currently a Professor, Director of the Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. Dr. Hu has published more than 170 papers in the journals, such as Lancet Oncology, JCO, and International Journal Cancer, and 5 book chapters. He is vice editor of the ABC (Advanced breast cancer) guideline (Chinese version) and one of the leading authors of the CBCS (Chinese Breast Cancer Society) guideline for breast cancer diagnosis and treatment which is updated biannually.

Dr. Hu is an active member of the American Society of Clinical Oncology, General secretary & Member of the standing committee of CBCS (Chinese Breast Cancer Society), Vice-chair of Shanghai Breast Cancer Society, Member of the Standing Academic Committee of CSCO (Chinese Society of Clinical Oncology).

Dr. Hu’s major interest is in the diagnosis and management of breast cancer, both in the clinic and in the laboratory, and in phase I trial on new anticancer agents. His laboratory interests and contributions have been in the area of serum tumor markers, epigenetic alteration and gene expression, and detection of residual disease. He and his laboratory are now concentrating on translational research on triple-negative breast cancer and angiogenesis.