Researchers fromUCLA Jonsson Comprehensive Cancer Center presented research at the Breast Cancer Symposium of San Antonio showing that a subgroup analysis of one phase III study found a consistent benefit in progression-free survival (PFS) and objective response rate (ORR) when women diagnosed with HER2-positive metastatic breast cancer were treated with anti-HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd), compared to the current standard of treatment.
Although consistent PFS and ORR benefits were observed in various subgroups, the therapy appeared to be surprisingly effective in controlling intracranial tumors in patients who had brain metastases stable when they joined the studio.
The confirmed objective response rate for breast cancer was more than three times higher in these patients with brain metastases treated with study drug than in those receiving standard treatment, according to the experts, who presented their findings at a General Presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS). Median progression-free survival in patients with brain metastases was 15 months in the trastuzumab deruxtecan arm compared to three months in the standard treatment arm.
Trastuzumab deruxtecan: here are the effects obtained with the T-DXd treatment
The researchers stated that the confirmed responses and partial responses observed in the brain suggest that treatment is associated with a substantial intracranial tumor response and reduction of nervous system diseaseor central.
Of the 36 patients with brain metastases treated with trastuzumab deruxtecan, 63.9% had a brain metastatic response, of which 10 had a complete response. This was compared favorably with the results in 36 patients with brain metastases treated with trastuzumab emtansine (T-DM1) (33.4% intracranial response and one complete response).
“The primary goals in the treatment of HER2-positive metastatic breast cancer, including those with stable brain metastases, are to improve symptoms, stabilize or reduce tumor size, and improve overall survival.and ”, said the first author, Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Research Program at theUCLA Jonsson Comprehensive Cancer Center.
“The increased efficacy seen in DESTINY-Breast 03 in the subgroup of patients with stable brain metastases at baseline in this study is encouraging and may provide another potential option for patients who have experienced disease progression with currently available therapies,” the scientist specified.
DESTINY-Breast03 is a Phase III clinical study evaluating T-DXd, a HER2-targeted monoclonal antibody that delivers high concentrations of chemotherapy directly to cancer cells that have the HER2 protein on their surface.
The primary study results, reported in September, found that treatment significantly prolonged progression-free survival compared to standard treatment. “This data is nothing short of phenomenal and the practice will change,” Hurvitz said at the time.
Up to 20% of breast cancers are classified as HER2 positive, which means the tumor has extra copies of the gene for HER2 and too much HER2 protein on the cell surface, which causes the cancer to behave more aggressively, leading to worse outcomes, including a greater chance of metastasis.
The development of HER2-targeted treatments, such as trastuzumab, pertuzumab, and T-DM1, has significantly improved outcomes, but most patients with advanced disease will experience resistance and disease progression despite these targeted therapies.
The first-line standard of care for patients with HER2-positive metastatic breast cancer is HER2 antibody therapy with pertuzumab / trastuzumab, plus chemotherapy. If the cancer progresses, the standard care since 2013 has been to switch to T-DM1 therapy, which is an antibody-drug conjugate consisting of trastuzumab and chemotherapy.
The primary results of the DESTINY-Breast03 study showed that Trastuzumab deruxtecan is significantly better than T-DM1 when used after a patient’s disease has progressed with trastuzumab and chemotherapy.
Hurvitz said these data support T-DXd as a standard second-line therapy for metastatic disease, as recently recommended in new guidelines published by the National Comprehensive Cancer Network (NCCN).
There Food and Drug Administration gave accelerated approval for the drug in 2019 for breast cancer patients with unresectable or metastatic HER2-postive who have received two or more prior HER2-based therapies in the metastatic setting.
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