Enhertu Recommended for EU Approval in HER2-Positive Metastatic Breast Cancer, Demonstrating Superior Efficacy Over Kadcyla

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News on June 28, 2022 /BioValleyBIOON/ -- AstraZeneca and Daiichi Sankyo recently announced jointly that the European MedicinesManagementThe Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive review opinion, recommending approval.Enhertu (trastuzumab deruxtecan): As a monotherapy for the treatment of unresectable or metastatic HER2-positive patients who have previously received one or more anti-HER2 regimens.Breast CancerAdult patients.Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which is expected to make a final decision in the third quarter of 2022.In the United States, Enhertu was approved for the aforementioned indication in May this year.

Enhertu is a HER2-targeted antibody-drug conjugate (ADC) developed through a collaboration between AstraZeneca and Daiichi Sankyo. Breast cancer remains the most common cancer worldwide, with 2020 data showing...DiagnosisMore than 2 million cases have been reported, resulting in nearly 685,000 deaths globally. In Europe, over 530,000 cases are diagnosed annually.Approximately one in five breast cancer cases are considered HER2-positive. Despite initial treatment with trastuzumab and taxanes, patients with HER2-positive metastatic breast cancer typically experience disease progression., more effective treatment options are needed to further delay disease progression and prolong survival.

The positive review opinion of the CHMP is based on the results of the groundbreaking head-to-head Phase 3 DESTINY-Breast03 trial:In patients with HER2-positive unresectable and/or metastatic breast cancer who have previously received trastuzumab and taxane therapy,Compared with Roche's HER2-targeted ADC product Kadcyla (trastuzumab emtansine, T-DM1), Enhertu reduced the risk of disease progression or death by 72% (95% CI: 0.22-0.37; p<0.0001).

Kadcyla is a targeted drug 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 previously treated with currently available HER2-targeted therapies typically experience disease progression in less than a year. In the DESTINY-Breast03 trial,Patients receiving Enhertu treatment demonstrated consistently significant benefits across various efficacy endpoints and key subgroups, supporting the potential of Enhertu as a new standard of care for this group of patients with HER2-positive metastatic breast cancer.

Detailed positive results from the DESTINY-Breast03 trial were presented in September 2021 at the European Society for Medical Oncology (ESMO) Virtual Congress, showing that Enhertu demonstrated a significant efficacy advantage over Kadcyla in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. Substantial and consistent benefits were observed across multiple efficacy endpoints and key subgroups.

The data disclosed at the meeting showed that, in the pre-specified interim analysis, the DESTINY-Breast03 trial met the primary endpoint of progression-free survival (PFS):Compared with Kadcyla, Enhertu significantly reduced the risk of disease progression or death by 72% (HR=0.28; 95% CI: 0.22-0.37; p=7.8x10E-22). After follow-ups of 15.5 months for the Enhertu group and 13.9 months for the Kadcyla group, the median PFS for patients in the Enhertu group had not yet been reached (95% CI: 18.5-NE), while the median PFS for patients in the Kadcyla group was 6.8 months (95% CI: 5.6-8.2).

In the key secondary endpoint of investigator-assessed PFS, the median PFS in the Enhertu group was three times that of the Kadcyla group (25.1 months vs 7.2 months; HR=0.26; 95% CI: 0.20-0.35; p=6.5x10E-24).Consistent PFS benefits were observed in key subgroups of patients receiving Enhertu, including those with a history of stable brain metastases.

Moreover, in terms of the key secondary endpoint, overall survival (OS): compared with the Kadcyla group,The Enhertu group showed a strong trend towards OS improvement (HR=0.56; 95% CI: 0.36-0.86; nominal p=0.007172),But this analysis is still immature, and there is noStatisticsStatistical significance. Nearly all patients in the Enhertu group survived after one year (94.1%), compared to a survival rate of 85.9% in the Kadcyla group.

Compared with the Kadcyla group, the confirmed objective response rate (ORR) in the Enhertu group was more than doubled (79.7% vs 34.2%).In the Enhertu group, 42 cases (16.1%) of complete response (CR) and 166 cases (63.6%) of partial response (PR) were observed, while in the Kadcyla group, 23 cases (8.7%) of complete response (CR) and 67 cases (25.5%) of partial response (PR) were observed.

In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. The most common ≥Grade 3 treatment-emergent adverse events in the Enhertu group were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%), and nausea (6.6%). According to the Independent Review Committee, there were 27 cases (10.5%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported. The majority (9.7%) were low-grade (Grade 1 or 2), with two Grade 3 (0.8%) events reported. No Grade 4 or Grade 5 ILD or pneumonitis events occurred.

In March 2019, AstraZeneca and Daiichi Sankyo reached a deal worth $6.9 billion in total.ImmunityOncology collaboration to jointly develop Enhertu for treating cancer patients with various HER2 expression levels or HER2 mutations, includingStomach Cancer、Colorectal CancerAndLung CancerHER2-low breast cancer.

Enhertu is a next-generation ADC drug that links the HER2-targeted humanized monoclonal antibody trastuzumab (Herceptin) 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 adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. Additionally, Enhertu (6.4mg/kg) has also been approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received a trastuzumab-based regimen.

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 among patients with HER2-positive metastatic breast cancer. This disease is still incurable, and patients eventually experience disease progression after receiving currently available therapies.HER2 is a tyrosine kinase receptor pro-growth protein expressed on the surface of various tumor cells, including gastric cancer, breast cancer, lung cancer, and colorectal cancer, and is associated with aggressive disease and poor prognosis.(Bioon.com)

Source of Original Text:Enhertu recommended for approval in the EU by CHMP for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen