ENHERTU Demonstrates Superior Efficacy Over Kadcyla Across Multiple Subgroups in Phase 3 DESTINY-Breast03 Trial for HER2-Positive Metastatic Breast Cancer

December 13, 2021 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) and Daiichi Sankyo recently at the 2021 San AntonioBreast CancerThe groundbreaking head-to-head phase 3 DESTINY-Breast03 trial of Enhertu (trastuzumab deruxtecan-nxki) was presented at the SABCS conference.New data further reinforces Enhertu's breakthrough efficacy in treating HER2-positive metastatic breast cancer patientsEnhertu is an antibody-drug conjugate (ADC) targeting HER2, jointly developed by AstraZeneca and Daiichi Sankyo. In October this year, based on preliminary data from the DESTINY-Breast03 trial, the U.S. FDA granted Enhertu Breakthrough Therapy Designation (BTD). To date,Enhertu has been approved in the United StatesFDAGranted 4 BTDs, 2 of which are for the treatment of breast cancer。

The data presented at this meeting showed that: in HER2-positive unresectable and/or metastatic breast cancer patients previously treated with trastuzumab and taxanes, compared with Roche's HER2-targeted ADC productKadcyla (Hershey), ado-trastuzumab emtansine, T-DM1) compared with,Enhertu Demonstrates Higher Progression-Free Survival (PFS) and Objective Response Rate (ORR) in Prespecified Patient SubgroupsIn patient subgroups defined by stable brain metastases, hormone receptor status, number of prior treatment lines, prior Perjeta (pertuzumab) treatment, and visceral metastasis status, similar PFS and ORR benefits were observed.

InAmong patients with stable brain metastases at baseline, Enhertu showed higher PFS compared to Kadcyla.(Progression-Free Survival (PFS) Hazard Ratio [HR] per Blinded Independent Central Review (BICR) = 0.25; 95% CI: 0.13-0.45). Additionally, in this subgroup, the median PFS was 15 months in the Enhertu treatment group compared to 3 months in the Kadcyla treatment group.

30%-50% of patients with HER2-positive metastatic breast cancer will develop brain metastases. Although the increased availability of HER2 therapies has improved systemic disease control, the prognosis after brain metastasis remains poor.

At baseline examination,The confirmed ORR for stable brain metastasis patients was 67.4%, compared to 20.5% in the Kadcyla treatment group.. In stable brain metastasis patients who underwent scans at baseline, a retrospective, non-pre-specified assessment of intracranial response provided preliminary evidence suggesting that treatment with Enhertu is associated with intracranialTumorAssociated with the alleviation and reduction of central nervous system diseases, 10 patients (27.8%) achieved complete response (CR), 13 (36.1%) achieved partial response (PR), while in the Kadcyla treatment group, 1 patient (2.8%) achieved CR and 11 (30.6%) achieved PR.

In the DESTINY-Breast03 study, the most common adverse events with Enhertu treatment were consistent with prior Enhertu studies in breast cancer.Clinical TrialConsistent, no new safety issues were identified. Drug-related interstitial lung disease or pneumonia was reported in 27 cases (10.5%) in the Enhertu group and 5 cases (1.9%) in the Kadcyla group, with no Grade 4/5 events.

In March 2019, AstraZeneca and Daiichi Sankyo reached a $6.9 billion immunotherapy agreement.TumorCollaborate to jointly develop Enhertu for the treatment of various cancer patients with different HER2 expression levels or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and HER2-low breast cancer.

Enhertu is a next-generation ADC drug that links the HER2-targeted humanized monoclonal antibody trastuzumab (曲妥珠单抗) with a novel topoisomerase 1 inhibitor exatecan derivative (DX-8951 derivative, DXd) through a 4-peptide linker, enabling the targeted delivery of cytotoxic agents into cancer cells and reducing systemic exposure to cytotoxic agents compared with conventional chemotherapy.

To date, Enhertu (5.4mg/kg) has been approved in multiple countries as a monotherapy for the treatment of unresectable or metastatic HER2-positive disease in patients who have received two or more prior anti-HER2-based treatment regimens in the metastatic setting.HER2-Positive Breast CancerAdult patients. In addition, Enhertu (6.4mg/kg) has also been approved in multiple countries: for the treatment of locally advanced or metastaticHER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinomaAdult patients.

Breast cancer is the most common type of cancer in women and one of the leading causes of cancer-related deaths in women. Approximately 20% of breast cancer cases are HER2-positive. Despite recent advancements in treatment and the approval of several new drugs, there remains a significant unmet clinical need in patients with HER2-positive metastatic breast cancer. This disease remains incurable, and patients eventually experience disease progression after receiving currently available therapies. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on variousTumorCell surface, including gastric cancer, breast cancer, lung cancer, and colorectal cancer, is associated with invasive disease and poor prognosis.

Kadcyla is a targeted drug that has been approved for the treatment of HER2-positive breast cancer patients mentioned above. DESTINY-Breast03 is the first global Phase 3 head-to-head trial comparing Enhertu with a positive control drug. HER2-positive metastatic breast cancer patients who have been previously treated typically experience disease progression in less than a year when treated with currently available HER2-targeted therapies. In the DESTINY-Breast03 trial,Patients treated with Enhertu showed consistently high and significant benefits across various efficacy endpoints and key subgroups., thisSupports the potential of Enhertu as a new standard of care for patients with HER2-positive metastatic breast cancer.(Bioon.com)

Source of Original Text:ENHERTU (fam-trastuzumab deruxtecan-nxki) Additional Analyses Further Reinforce Ground-breaking Efficacy in Patients With HER2-positive Metastatic Breast Cancer