AstraZeneca, Daiichi Sankyo Move the Bar in Metastatic Breast Cancer

Advanced breast cancer

AstraZeneca and Daiichi Sankyo aim to reshape the metastatic breast cancer care landscape with the antibody-drug conjugate Enhertu. Data presented at the American Society of Clinical Oncology meeting this weekend show that treatment with Enhertu demonstrated a 49% improvement in median overall survival by more than six months compared to chemotherapy alone.

Data from the DESTINY-Brest04 study, which included 557 patients, is being touted as groundbreaking, as Enhertu is the first HER-2-directed therapy to demonstrate a survival benefit in this population, potentially redefining treatment for approximately half of all patients with breast cance. Breast cancer is the most common cancer globally, with more than two million cases diagnosed in 2020. It is estimated that about half of all breast cancer patients have tumors that express HER-2, either positive or negative. HER2 testing is routinely used to determine appropriate treatment options for patients with breast cancer. 

Gilles Gallant, senior vice president and global head of oncology clinical development at Daiichi Sankyo told BioSpace that these patients have tumors with a HER2 IHC score of 1+, or a HER2 IHC score of 2+ in combination with a negative ISH test, an expression level that is not currently eligible for HER2 targeted therapy.

DESTINY-Breast04 is the first Phase III trial of a HER2 directed therapy that showed a “significant and clinically meaningful survival benefit in previously treated patients with HER2 low unresectable and/or metastatic breast cancer,” he said. Gallant added that data from the study indicates a need to “change the way we classify and treat metastatic breast cancer to ensure these patients are effectively diagnosed and treated.”

Enhertu is an antibody-drug conjugate comprised of a humanized anti-HER2 IgG1 monoclonal antibody. It has previously been approved as a treatment for adults with unresectable or metastatic HER2-positive breast cancer who have had two or more previous anti-HER2-based therapies in the metastatic setting. 

In 2021, Enhertu became the first HER2-directed medication approved to treat gastric cancer in the U.S. in the last ten years. Specifically, it was approved for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

AstraZeneca and Daiichi Sankyo noted that targeting the lower range of expression in the HER-2 spectrum may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer. Currently, patients with low HER-2 positive tumors have limited treatment options after their disease progresses on endocrine therapy. Additionally, the companies said there are few targeted options for those patients who are HER-2 negative.

Results presented at ASCO showed Enhertu (trastuzumab deruxtecan) provided “superior and clinically meaningful progression-free survival and overall survival” in breast cancer patients with hybridization (ISH)-negative) unresectable and/or metastatic breast cancer with hormone receptor (HR) positive or HR-negative disease compared to standard of care treatment, physician’s choice or chemotherapy. 

Overall, data from the study showed a 49% reduction in the risk of disease progression or death compared to the control treatments. Median progression free survival was 10.1 months for Enhertu compared to 5.4 months. Also, the data showed a 36% reduction in the risk of death for those who were treated with Enhertu compared to chemotherapy in patients with HR-positive disease. The median overall survival for Enhertu-treated patients in this group was 23.9 months compared to 17.5 months with chemotherapy.

“Today’s results represent a pivotal moment demonstrating the potential for Enhertu to redefine the treatment of HER2-targetable cancers. DESTINY-Breast04 validates targeting the lower end of the spectrum of HER2 expression, since Enhertu reduced the risk of disease progression or death across all types of patients in the trial by half, and reduced the risk of death by over a third. We must now evolve the way we classify and treat metastatic breast cancer to ensure these patients are effectively diagnosed and treated,” Susan Galbraith, head of oncology R&D at AstraZeneca, said in a statement. 

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