A year of treatment with trastuzumab emtansine (T-DM1; Kadcyla®; Genentech/Roche), a drug made of an antibody linked to a chemotherapeutic drug, has proven highly effective in preventing stage 1 Human epidermal growth factor receptor 2 (HER2)-positive breast cancer from recurring in patients. This is the conclusion of a study by team led by Dana-Farber Cancer Institute researchers.

In the ATEMPT trial, supported by Genentech, Gloria Spivak Faculty Advancement Fund, and Susan G. Komen, 512 patients with the earliest stage of breast cancer that tested positive for the HER2 protein, 97% were treated with adjuvant trastuzumab emtansine (after surgery). These patients were alive and free of invasive cancer five years after treatment.[1]

The results of the study were published online in the Journal of Clinical Oncology. The study outcomes suggest that trastuzumab emtansine is a reasonable treatment approach for this stage 1 population. [1]

The outcomes of the ATEMPT-study confirm the trial’s primary analysis which found that one year of adjuvant trastuzumab emtansine (T-DM1) achieved a 3-year iDFS of 97.8% for patients with stage I HER2+ breast cancer, but was not associated with fewer clinically relevant toxicities (CRTs) compared with paclitaxel and trastuzumab. These results were presented during the 2022 San Antonio Breast Cancer Symposium (SABCS) and published in Cancer Research. [2][3]

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In conjunction with the trial, researchers looked for biomarkers of whether the cancer was likely to recur even after treatment with trastuzumab emtansine. They found that patients with high scores on the HER2DX test* – which weighs clinical factors and the activity of four genes within tumor tissue – had a greater risk of recurrence.

Paolo Tarantino, MD is a Clinical Research Fellow at the Dana-Farber Cancer Institute (Boston, Massachusetts) and a researcher at the European Institute of Oncology (Milan, Italy). His main areas of research are breast cancer, HER2 oncogene and antibody-drug conjugates. Photo courtesy: © 2024 Dana-Farber Cancer Institute. Used with permission.

“Patients with stage 1 HER2-positive breast cancer have recurrence rates of 5 to 30%. Post-surgical treatment with chemotherapy and the antibody trastuzumab, which binds to HER2, can significantly reduce the risk of recurrence in these patients. But the side effects can have a detrimental impact on patients’ quality of life,” noted study lead author Paolo Tarantino, MD, of Dana-Farber and the University of Milan (Italy).

“In this study, we evaluated trastuzumab emtansine, which links trastuzumab to a powerful chemotherapy agent (known as DM1), for effectiveness and toxicity in this group of patients,” Tarantino further noted.

Trastuzumab emtansine is an antibody-drug conjugate or ADC which is currently approved for post-surgical, or adjuvant, treatment of patients with HER2-positive breast cancer which remains after pre-surgical treatment.  The agent is also approved for patients with metastatic HER2-positive breast cancer. The new study, a randomized phase 2 clinical trial dubbed ATEMPT, involved patients with a stage 1 HER2-positive cancer, meaning it was small and without lymph node involvement.

Sara M. Tolaney, MD, MPH, is a breast medical oncologist at Dana-Farber Cancer Institute whose research focuses on the development of novel therapies in the treatment of breast cancer. She has been instrumental in developing several treatment approaches for breast cancer, including approaches focused on tailoring therapy for early stage HER2+ disease, use of cdk 4/6 inhibitors, antibody drug conjugates, and immunotherapy. Photo courtesy: © 2024 Dana-Farber Cancer Institute. Used with permission.

The trial enrolled 512 patients at cancer centers across the U.S.: 384 of the participants were treated with trastuzumab emtansine and 128 were treated with chemotherapy and trastuzumab. Investigators found that, five years after treatment, 97% of patients receiving T-DM1 had no evidence of cancer recurrence.

The rate of clinically relevant toxicities was similar in the trastuzumab emtansine group and the chemotherapy-and-trastuzumab group. However, patient-reported outcomes from this study shower better quality of life with trastuzumab emtansine, that was associated with less neuropathy, less hair loss and better work productivity than chemotherapy and trastuzumab.

Results of HER2DX testing showed that patients whose risk score was above an established threshold had a significantly higher chance of a cancer recurrence.

“The ATEMPT trial has taught us that one year of trastuzumab emtansine after surgery for patients with a stage 1 HER2-positive cancer leads to outstanding long term outcomes, making it a reasonable treatment approach for select patients,” concluded senior author Sara Tolaney, MD, MPH, Chief, Division of Breast Oncology, Dana-Farber Cancer Institute.


Note * The HER2DX test is a prognostic and predictive assay in early-stage HER2-positive breast cancer based on clinical features and the expression of 4 gene signatures (immune, proliferation, luminal differentiation and HER2 amplicon), including ERBB2 mRNA levels. The test is developed by Reveal Genomics.

Clinical trials
T-DM1 vs Paclitaxel/​Trastuzumab for Breast (ATEMPT Trial) – ClinicalTrials.gov ID NCT01853748
ATEMPT 2.0: Adjuvant T-DM1 vs TH – ClinicalTrials.gov ID NCT04893109

Highlights of prescribing information
Trastuzumab emtansine (T-DM1; Kadcyla®; Genentech/Roche) [Prescribing Information]


[2] Khattak MN, Chichura AM, Lang JE. Adjuvant Trastuzumab Emtansine Versus Paclitaxel and Trastuzumab in Stage I HER2-Positive Breast Cancer: The ATEMPT Trial. Ann Surg Oncol. 2024 Mar;31(3):1423-1427. doi: 10.1245/s10434-023-14766-9. Epub 2023 Dec 21. PMID: 38127215.
[3] Paolo Tarantino, Nabihah Tayob, Chau T Dang, Denise Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, R. Adjuvant Trastuzumab Emtansine Versus Paclitaxel plus Trastuzumab for Stage I HER2+ Breast Cancer: 5-year results and correlative analyses from ATEMPT (TBCRC033) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-01.

Featured Image: Women and the power to fight breast cancer Courtesy: © 2017 – 2024. Fotolia/Adobe. Used with permission.


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