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Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study

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Abstract

Purpose

In the KATHERINE study (NCT01772472), patients with HER2-positive early breast cancer (EBC) and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy who were treated with adjuvant trastuzumab emtansine (T-DM1) had a 50% reduction in the risk of an invasive disease-free survival (IDFS) event compared to patients treated with adjuvant trastuzumab. In metastatic disease, T-DM1 has resulted in higher rates of thrombocytopenia in Asian versus non-Asian patients. Here, we report safety and efficacy in Chinese patients from KATHERINE.

Methods

Patients with HER2-positive EBC and residual invasive disease after taxane- and trastuzumab-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 or trastuzumab. The primary endpoint was time to an IDFS event.

Results

Among Chinese patients (T-DM1 n = 51, trastuzumab n = 50), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR = 0.57; 95% CI 0.25–1.31), with similar results for secondary endpoints. As in the global population, Chinese patients receiving T-DM1 versus trastuzumab had more grade ≥ 3 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade ≥ 3 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade ≥ 3 hemorrhage was reported in 1 patient (T-DM1 arm).

Conclusions

In the KATHERINE study, T-DM1 demonstrated increased efficacy compared to trastuzumab in Chinese patients. Consistent with previous data in Asian patients, T-DM1 was associated with more grade ≥ 3 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.

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Data availability

Qualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Acknowledgements

This trial was sponsored by F. Hoffmann-La Roche, Ltd. Medical writing assistance was provided by Andrea Bothwell, B.Sc., and Holly Strausbaugh, Ph.D., on behalf of Twist Medical.

Funding

This research was funded by F. Hoffmann-La Roche, Ltd.

Author information

Authors and Affiliations

  1. National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Chiun-Sheng Huang

  2. Taichung Veterans General Hospital and School of Medicine, China Medical University, Taichung City, Taiwan

    Youngsen Yang

  3. Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Ava Kwong

  4. Chang Gung Memorial Hospital, Chang Gung University Medical College, Taoyuan, Taiwan

    Shin-Cheh Chen

  5. Taipei Veterans General Hospital, Taipei, Taiwan

    Ling-Ming Tseng

  6. Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan

    Mei-Ching Liu

  7. Shanghai Jiaotong University School of Medicine, Ruijin Hospital, Shanghai, China

    Kunwei Shen

  8. Sun Yat-Sen University Cancer Center, Guangdong Sheng, China

    Shusen Wang

  9. Tuen Mun Hospital, Tuen Mun, Hong Kong

    Ting-Ying Ng

  10. Roche (China) Holding Ltd., Shanghai, China

    Yi Feng, Guofang Sun & Iris Renfei Yan

  11. Fudan University Shanghai Cancer Center, No. 270, Dongan Road, Shanghai, 200032, China

    Zhimin Shao

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Contributions

The authors developed the first draft of the manuscript with help from a medical writer funded by F. Hoffmann-La Roche Ltd. All authors had full access to all of the data in the study, contributed to data interpretation, contributed to manuscript drafts, and approved the final draft of the manuscript for journal submission.

Corresponding author

Correspondence to Zhimin Shao.

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Conflict of interest

All authors received third-party writing assistance which was funded by F. Hoffmann-La Roche, Ltd. Chiun-Sheng Huang’s institution has received research funding from AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, OBI Pharma, Pfizer, and Roche. He has served on advisory boards for Amgen, Astra Zeneca, Daiichi Sankyo, Eli Lilly, Pfizer, Roche. He has received travel expenses from Amgen, Astra Zeneca, Pfizer, and Roche. He has received speaker honoraria from AstraZeneca, Eli Lilly, Novartis, Pfizer, and Roche. Youngsen Yang’s institution has received research funding from Astellas, Celgene, Eli Lilly, Janssen, Mundipharma, Novartis, Ono, Orient Europharma, and Roche. Ava Kwong’s institution has received research funding from Merck, Novartis, Roche, and WKK Medical Equipment Company, Ltd. She has received speaker and/or consulting honoraria from AstraZeneca, Pfizer, Roche, and Stryker. Shin-Cheh Chen has nothing to disclose. Ling-Ming Tseng’s institution has received research funding from Novartis, Pfizer, and Roche. He has served on advisory boards for Amgen, Eli Lily, Novartis, Daiichi Sankyo, and Roche. He has received travel expenses from AstraZeneca, Novartis, Pfizer, and Roche. He has received speaker honoraria from Pfizer and Roche. Mei-Ching Liu has served on advisory boards for AstraZeneca and Roche. Kunwei Shen has nothing to disclose. Shusen Wang has nothing to disclose. Ting-Ying Ng has nothing to disclose. Yi Feng, Guofang Sun, and Iris Renfei Yan are employees of Roche (China) Holding Ltd. Zhimin Shao has nothing to disclose.

Ethical approval

The study protocol was approved by the institutional review board at each study site. The trial was conducted in accordance with the ethical standards of each institution and applicable national standards as well as in accordance with the amended Declaration of Helsinki.

Informed consent to participate

Informed consent forms were approved by each study site’s Institutional Review Board (IRB)/Ethical Committee (EC). Signed written informed consent forms were required of each patient before they could participate in the study. Patients could withdraw consent at any time.

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Huang, CS., Yang, Y., Kwong, A. et al. Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study. Breast Cancer Res Treat 187, 759–768 (2021). https://doi.org/10.1007/s10549-021-06166-y

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