Health Canada expands approval of Enhertu™ for adults with HER2-positive metastatic breast cancer

Approval based on the ground-breaking DESTINY-Breast03 Phase III trial, showing Enhertu reduced the risk of disease progression or death by 72 per cent compared to standard of care

MISSISSAUGA, ON, June 23, 2022 /CNW/ - On June 15, 2022 Health Canada approved Enhertu™ (trastuzumab deruxtecan) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have received at least one prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and developed disease recurrence during or within six months of completing neoadjuvant or adjuvant therapy.¹

The approval was based on results from the head-to-head DESTINY-Breast03 Phase III trial first presented at the European Society for Medical Oncology (ESMO) Congress in September 2021, and recently published in The New England Journal of Medicine,² showing Enhertu was significantly better than the current standard of care (trastuzumab emtansine or T-DM1) in reducing the risk of disease progression or death.

"Clinical trials of Enhertu have consistently shown remarkable efficacy in extending progression-free survival over the current standard of care for persons with advanced HER2-positive breast cancer," said Dr. Karen Gelmon, Professor of Medicine, University of British Columbia and Medical Oncologist, BC Cancer. "The expanded indication for Enhertu by Health Canada marks an important advancement in providing persons living with metastatic breast cancer and physicians with a much-needed and effective option earlier in the metastatic setting."

In Canada, 10 per cent of newly diagnosed breast cancers are metastatic, and for those initially diagnosed with early-stage breast cancer, approximately 30 per cent will progress to metastatic disease.³ HER2-positive breast cancer tends to be a more aggressive sub-type of breast cancer, comprising about one in five cases of breast cancer.⁴

"Despite advancements made in metastatic breast cancer, women with HER2-positive metastatic breast cancer remain underserved, and it is crucial that these women have newer, more effective treatments as soon as possible," said Cathy Ammendolea, Chair of the Board, Canadian Breast Cancer Network. "We're thrilled to see the approval of a new option that could help women with this type of cancer live longer, better lives."

In the DESTINY-Breast03 trial, Enhertu demonstrated a 72 per cent reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p=7.8x10^-22) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) per blinded independent central review was not reached (95% CI 18.5, NE) in the Enhertu arm and 6.8 months in the T-DM1 arm (5.6, 8.2). At the time of the PFS analysis, 16.4 per cent of patients had died and overall survival (OS) was immature. Confirmed objective response rate (ORR) was more than double in the Enhertu arm versus the T-DM1 arm (79.7% (95% CI 74.3, 84.4) vs. 34.2% (95% CI 28.5, 40.3).¹  

"Many young patients with HER2-positive metastatic breast cancer face the reality of living condensed lives. They live with uncertainty and hope for new treatments that will allow them to live longer with a good quality of life," said MJ DeCoteau, Executive Director and Founder of Rethink Breast Cancer. "For them, a treatment like Enhertu could be a game-changer. The exciting news that it's significantly more effective than our current standard therapy has the metastatic HER2 community buzzing. It means more hope for making milestones, achieving bucket lists and spending quality time with families and loved ones."

About DESTINY-Breast03 Trial
DESTINY-Breast03 is a global head-to-head, randomized, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4 mg/kg) versus T-DM1 (3.6 mg/kg) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, PFS based on investigator assessment and safety.

The safety profile of Enhertu was generally consistent with previous clinical trials. The most common adverse reactions (frequency ≥20%) were nausea, fatigue, vomiting, neutropenia, alopecia, constipation, anemia, transaminases increased, musculoskeletal pain, leukopenia, decreased appetite, diarrhea, thrombocytopenia, headache, and abdominal pain. The most common serious adverse reactions (frequency >1%) were interstitial lung disease (ILD) and vomiting. Overall, 10.5 per cent of patients had ILD or pneumonitis related to treatment as determined by an independent adjudication committee. Most ILD events were Grade 1 (2.7%) or Grade 2 (7.0%). Two Grade 3 (0.8%) events were reported. No Grade 4 or Grade 5 ILD or pneumonitis events were reported.¹

DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. 

About Enhertu
Enhertu is a HER2-directed antibody-drug conjugate (ADC), which consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. Enhertu was first approved in Canada in 2021 for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received prior treatment with trastuzumab emtansine based on the results from the DESTINY-Breast01 trial.  

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 & Metabolism (CVRM), and Respiratory & Immunology. The company employs roughly 1,200 people across Canada, including 700 employees at our head office and clinical research hub in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.  

REFERENCES

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^1	Enhertu Product Monograph, June 15, 2022.
^2	Cortes J, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med 2022; 386:1143-1154.
^3	Canadian Breast Cancer Network. Metastatic Breast Cancer in Canada Infographic. Available at: https://www.cbcn.ca/en/metastatic_infographic  Accessed March 17, 2022.
^4	Mayo Clinic. HER2-Positive Breast Cancer: What Is It? Available at: https://www.mayoclinic.org/breast-cancer/expert-answers/faq-20058066 Accessed March 17, 2022.

SOURCE AstraZeneca Canada Inc.

Vanessa Principe, AstraZeneca Canada, E-mail: [email protected]