ENHERTU® approved in Canada as the first and only HER2-directed therapy for patients with HR-positive HER2-low or HER2-ultralow metastatic breast cancer, following disease progression after one or more endocrine therapies

Based on the DESTINY-Breast06 phase III trial results demonstrating statistically significant and clinically meaningful progression-free survival benefit in patients treated with Enhertu vs. conventional chemotherapy 

MISSISSAUGA, ON, Oct. 29, 2025 /CNW/ - Health Canada has granted a Notice of Compliance (NOC) for Enhertu^® (trastuzumab deruxtecan) for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting and are not considered suitable for endocrine therapy as the next line of treatment.¹

The approval is based on positive results from the phase III DESTINY-Breast06 trial, presented at the 2024 American Society of Clinical Oncology (ASCO) Meeting and published in The New England Journal of Medicine.² In the DESTINY-Breast06 trial, Enhertu showed a 36% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.54,0.76; p<0.0001) in the overall trial population of patients with chemotherapy-naïve HER2-low or HER2-ultralow metastatic breast cancer.¹ Median progression-free survival (PFS) was 13.2 months (95% CI: 12.0, 15.2) in patients randomized to receive Enhertu compared to 8.1 months (95% CI: 7.0, 9.0) in patients randomized to receive chemotherapy.¹ The confirmed objective response rate (ORR) was 57.3% for the Enhertu arm and 31.2% for the chemotherapy arm.¹ Median duration of response (DOR) was 14.3 months (95% CI: 12.5-15.9) in the Enhertu arm versus 8.6 months (95% CI: 6.9-11.8) in the chemotherapy arm.¹ Efficacy outcomes refer to the overall (intention-to-treat) population as assessed by blinded independent central review; see Product Monograph for full study details.

"With this approval, chemotherapy-naïve patients with metastatic breast cancer whose tumours show low or ultralow HER2 expression now have access to a HER2-directed therapy following disease progression on endocrine therapy," said Dr. Christine Brezden-Masley, Medical Oncologist, Director of the Marvelle Koffler Breast Centre at Mount Sinai Hospital, and Medical Director of the Cancer Program for Sinai Health. "This development is based on data showing a reduction in disease progression compared to chemotherapy and supports the importance of reassessing HER2 status at the time of metastatic diagnosis to identify eligible patients that were previously considered HER2-negative."

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all cases.³ Despite being classified as HER2-negative, many of these tumours still have some level of HER2 expression detected by IHC.⁴ Currently, regardless of HER2 expression, endocrine-based therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer.^5,6 Following endocrine-based therapy, some patients discontinue treatment, and others are treated with conventional chemotherapy which is associated with poor response rates and outcomes.^6-8

"With recent research discoveries having identified new types of metastatic breast cancer called HER2-low and HER2-ultralow, now more people have innovative personalized cancer treatment options for better control of their disease," says Kimberly Carson, CEO, Breast Cancer Canada. "Today's announcement provides progress for patients while we seek timely, equitable access in Canada for all those with hormone receptor-positive HER2-low/ultralow types of metastatic breast cancer so they can benefit from the latest approval in cancer care."

HER2 status in the trial was confirmed by a central laboratory and was performed on a tumour sample obtained at the time of initial metastatic diagnosis or later.⁹ Approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer were determined to have actionable levels of HER2-expression.⁹ Further, nearly two-thirds of patients previously assessed as IHC 0 at a local laboratory were classified as HER2-low or HER2-ultralow upon central analysis of the tumour sample.⁹ In an exploratory analysis of patients with HER2-ultralow expression, results were seen to be consistent between patients with HER2-low expression and HER2-ultralow expression.⁹ 

The safety profile of Enhertu was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received Enhertu (5.4 mg/kg) in the DESTINY-Breast06 trial. The most common adverse reactions (frequency ≥20%) in patients treated with Enhertu were nausea, fatigue, alopecia, neutropenia, anemia, increased transaminases, diarrhea, vomiting, constipation, decreased appetite, leukopenia, COVID-19 and musculoskeletal pain. The most common serious adverse reactions (frequency >1%) were ILD, COVID-19, febrile neutropenia, hypokalemia. Three patients (0.7%) experienced fatal adverse reactions due to adjudicated drug-related interstitial lung disease (ILD). In addition, general physical health deterioration, neutropenic sepsis, and sepsis (0.2% each) were reported as drug-related fatal adverse reactions.¹

About Enhertu 

Enhertu is a HER2-directed antibody-drug conjugate. Designed using Daiichi Sankyo's proprietary DXd antibody drug conjugate (ADC) technology, Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

About DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus investigator's choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer.¹ Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months of starting treatment.¹

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), overall survival (OS) in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.² DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) in Asia, Australia, Europe, North America, including 10 sites in Canada, and South America.¹⁰ For more information about the trial, visit ClinicalTrials.gov.

About the Collaboration Between Daiichi Sankyo and AstraZeneca

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

About Daiichi Sankyo

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolic, and respiratory & immunology. In Canada, the company employs more than 2,500 people and was recently named one of Canada's Top 100 Employers for the second consecutive year. Together, AstraZeneca's R&D Hub and the Alexion Rare Disease R&D Hub – both based in Mississauga, Ontario – are involved in more than 150 global clinical studies in areas such as breast, lung and prostate cancer, COPD, chronic kidney disease, and rare disease. Visit www.astrazeneca.ca for more information. 

References:

1.	AstraZeneca Canada Inc., Enhertu^® (trastuzumab deruxtecan) Product Monograph. October 2025.
2.	Bardia A, et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391:2110-2122.
3.	National Cancer Institute. Surveillance, epidemiology and end results program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed April 2025.
4.	Breast Cancer Research Foundation. HER2-low breast cancer explained. Available at: https://www.bcrf.org/about-breast-cancer/her2-low-breast-cancer/. Accessed September 2025.
5.	Canadian Cancer Society. Hormone receptor status test. Available at: https://cancer.ca/en/treatments/tests-and-procedures/hormone-receptor-status-test#ci_hormone_receptor_status_test_89_8835_00. Accessed September 2025.
6.	Manohar P, et al. Updates in endocrine therapy for metastatic breast cancer. Cancer Biol Med. 2022; 19(2): 2020-212. Available at: https://www.cancerbiomed.org/content/19/2/202. Accessed October 2025.
7.	Cortes J, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914-923. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60070-6/fulltext. Accessed October 2025.
8.	Yuan P, et al. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer. 2019;112:57-65. Available at: https://www.sciencedirect.com/science/article/pii/S095980491930139X?via%3Dihub. Accessed October 2025.
9.	Salgado RF, et al. LBA21 - Human epidermal growth factor receptor 2 (HER2)-low and HER2-ultralow status determination in tumors of patients (pts) with hormone receptor–positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06). Ann. Oncol. 2024;35 (suppl_2):1-72.
10.	Clinicaltrials.gov. Study of trastuzumab deruxtecan (T-DXd) vs investigator's choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer (DB-06). Available at: https://clinicaltrials.gov/study/NCT04494425?cond=HER2-low%20Breast%20Cancer&term=DB-06&rank=1. Accessed September 2025.

SOURCE AstraZeneca Canada Inc.