Datopotamab Deruxtecan Promising in Breast Cancer
Data from the TROPION clinical studies began being released at the European Society of Medical Oncology (ESMO) Breast Cancer Virtual Congress and are regularly updated. The novel antibody drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) appears promising for the management of advanced breast cancers.
About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan is a precision cancer medicine known as an antibody drug conjugate (ADC). The anti-TROP2 (trophoblast cell-surface antigen 2) monoclonal antibody delivers topoisomerase I inhibitor cytotoxic chemotherapy (“payload”) directly to cancer cells via a linker attached to the monoclonal antibody that binds to TROP2 on cancer cells.
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is over expressed in several types of cancers, including breast cancer.4 Research indicates that high TROP2 expression is associated with cancer cell growth and poor patient survival.4,5 TROP2 is over expressed in approximately 80% of patients with TNBC, making it a promising target for precision cancer medicines.5
Triple-negative breast cancer
Approximately 12% of all breast cancers are TNBC, meaning that they are estrogen-receptor negative (ER-), progesterone-receptor negative (PR-), and human epidermal growth factor receptor 2-negative (HER2-). This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.
Unfortunately, many available and effective treatment options for the majority of breast cancers block the growth stimulating effects of ER, PR and/or HER2; therefore, TNBC has had limited therapeutic options. In addition, TNBC tends to be an aggressive type of cancer, is often diagnosed at a more advanced stage, and proportionately affects younger women more often than other breast cancers. Novel treatment options for TNBC have lagged behind that of other types of breast cancers. 1,2,3
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TROPION-PanTumor01Clinical Trial
The TROPION-PanTumor01 clinical trial was designed to evaluate the safety, tolerability, and preliminary effectiveness of datopotamab deruxtecan in patients with advanced cancers, including NSCLC and TNBC that are refractory to or relapsed from standard treatment or for whom no standard treatment is available.
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Dato-DXd resulted in a clinically meaningful improvement in cancer progression-free survival when directly compared with chemotherapy among patients with previously treated, hormone receptor-positive/HER2-negative inoperable or metastatic breast cancer, according to findings from the phase 3 TROPION-Breast01 trial. Overall 22% of Dato-DXd treated patients survived greater than one year without recurrent cancer compared to only 10% of those treated with chemotherapy.
HR-Positive, HER2 "low" or Negative Breast Cancer
The TROPION-Breast01 Phase III trial compared Dato-DXd to chemotherapy in women with advanced HR-positive, HER2-low or -negative breast cancer. In October 2023 preliminary trial results were released showing that that Dato-DXd demonstrated a clinically meaningful improvement in progression free survival compared to investigator's choice of chemotherapy. Overall, 37.5% of Dato-DXd treated patients survived without cancer progression 9 months from beginning treatment compared with 18.7% of those treated with chemotherapy.
In addition, compared to chemotherapy, Dato-DXd was associated with fewer significant side effects. The safety profile of Dato -DXd seen with breast cancer is consistent with safety that has been previously reported with lung cancer. The most common side effects are nausea, mucositis, fatigue, anemia and hair loss.
Accrual of additional patients is ongoing to the Tropion clinical trials and longer follow up is required to confirm these initial encouraging results. Dato-DXd may represent a significant advance in the management of triple negative and other breast cancers.
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CancerConnect was the first social network created for people with breast cancer. Founded by oncologists to support myeloma patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating breast cancer from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References:
- 1. American Cancer Society. Triple-negative breast cancer. Accessed April 19, 2021.
- Sharma P. Oncologist. 2016;21:1050-1062.
- National Cancer Institute. SEER cancer stat facts: female breast cancer subtypes. Accessed April 19, 2021.
- Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.
- Zaman S, et al. Onco Targets Ther. 2019;12:1781-1790
- Bianchini G, et al. Nat Rev Clin Oncol. 2016;13:674-690.
- Bray F, et al. CA Cancer J Clin. 2018;68:394-424.
- Bardia A, Jhaveri K, Im SA, et al. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: results from TROPION-Breast01. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract GS02-01
