Research table: Trastuzumab deruxtecan (Enhertu) for metastatic breast cancer treatment

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: Trastuzumab deruxtecan (Enhertu) is a HER2 antibody-drug conjugate. It consists of trastuzumab and the chemotherapy drug deruxtecan. Combining these drugs allows the targeted delivery of the chemotherapy to HER2-positive cancer cells.

Learn more about trastuzumab deruxtecan, including its side effects.

Trastuzumab deruxtecan and HER2-positive metastatic breast cancer

Trastuzumab deruxtecan is used to treat HER2-positive metastatic breast cancers that have progressed on past HER2-targeted therapy for metastatic breast cancer. It may help shrink these tumors and improve survival.

Trastuzumab deruxtecan and HER2-low metastatic breast cancer

Trastuzumab deruxtecan is also used to treat some HER2-low metastatic breast cancers. HER2-low breast cancers have low, but detectable, levels of HER2 expression.

Trastuzumab deruxtecan can increase survival better than standard chemotherapy in people who have HER2-low metastatic breast cancers that have progressed on chemotherapy, as well as those that have progressed on hormone therapy (but have not been treated with chemotherapy).

Trastuzumab deruxtecan and HER2-ultralow metastatic breast cancer

Trastuzumab deruxtecan is also used to treat some HER2-ultralow metastatic breast cancers. HER2-ultralow breast cancers have a faint amount of HER2 on the cell membranes (surfaces) of a small percentage of the cancer cells.

Trastuzumab deruxtecan can increase the time to cancer spread better than standard chemotherapy in people who have HER2-ultalow metastatic breast cancers that have progressed on hormone therapy.

Study selection criteria: For HER2-positive metastatic breast cancers: Clinical trials with 100 or more participants with HER2-positive metastatic breast cancer.

For HER2-low and HER2-ultralow metastatic breast cancers: Randomized clinical trials with 100 or more participants with HER2-low metastatic breast cancer or HER2-ultralow metastatic breast cancer.

Trastuzumab Deruxtecan and HER2-Positive Metastatic Breast Cancer
Study	Study Population (number of participants)	Drug(s) Used	Objective Response Rate—Percent who Responded to Treatment (95% CI)	Overall Survival at One Year (95% CI)
Clinical trials
DESTINY-Breast03 [1]	524	Trastuzumab deruxtecan	79% (73%-83%)	94%
		Trastuzumab emtansine	35% (29%-41%)	86%
DESTINY-Breast01 [2]	184	Trastuzumab deruxtecan	61% (53%-68%)	NA

NA = Not available

Trastuzumab Deruxtecan and HER2-low Metastatic Breast Cancer
Study	Study Population (number of participants)	Drug(s) Used	Objective Response Rate—Percent who Responded to Treatment (95% CI)	Overall Survival at One Year (95% CI)
Randomized clinical trials
DESTINY-Breast04 [3]	557*	Trastuzumab deruxtecan	52% (47%-57%)	74%
		Chemotherapy	16% (11%-23%)	57%
DESTINY-Breast06 [4]	713†	Trastuzumab deruxtecan	57% (51%-62%)	88%
		Chemotherapy	32% (27%-37%)	82%

* All participants had progressed on chemotherapy.

† All participants had progressed on hormone therapy, but they had not yet gotten chemotherapy in the metastatic setting.

Trastuzumab Deruxtecan and HER2-ultralow Metastatic Breast Cancer
Study	Study Population (number of participants)	Drug(s) Used	Objective Response Rate—Percent who Responded to Treatment (95% CI)	Overall Survival at One Year (95% CI)
Randomized clinical trials
DESTINY-Breast06 [4]	153†	Trastuzumab deruxtecan	62% (50%-73%)	NA
		Chemotherapy	26% (17%-38%)	NA

NA = Not available

† All participants had progressed on hormone therapy, but they had not yet gotten chemotherapy in the metastatic setting.

References

1. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 401(10371):105-117, 2023.
2. Modi S, Saura C, Yamashita T, et al. for the DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 382(7):610-621, 2020.
3. Modi S, Jacot W, Yamashita T, et al. for the DESTINY-Breast04 Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 387(1):9-20, 2022.
4. Bardia A, Hu X, Dent R, et al. for the DESTINY-Breast06 Trial Investigators. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med. 391(22):2110-2122, 2024.

Updated 02/14/25