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The antibody-drug conjugate shows efficacy in reducing disease progression risk and increasing progression-free survival in patients with HR+, HER2-low, or HER2-ultralow metastatic breast cancer.
The FDA approved trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) for the treatment of adults with unresectable or metastatic hormone receptor (HR)-positive (HR+), HER2-low, or HER2-ultralow breast cancer—determined by an FDA-approved test—that have progressed on 1 or more endocrine therapies, according to a news release from AstraZeneca.1
Image Credit: © David A Litman | stock.adobe.com
The HER2-directed antibody-drug conjugate (ADC) previously received priority review and breakthrough therapy designation from the FDA. In the DESTINY-Breast06 phase 3 trial, trastuzumab deruxtecan showed a 36% reduction in the risk of disease progression or death versus chemotherapy (HR 0.64; 95% CI: 0.54-0.76; P < .0001) in patients with chemotherapy-naïve HER2-low or HER2-ultralow metastatic breast cancer.1,2,3,4
“Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes,” Aditya Bardia, MD, MPH, investigator in the DESTINY-Breast06 trial, said in the news release. “With a median progression-free survival exceeding 1 year and a response rate of more than 60%, trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy.”1
In DESTINY-Breast06, patients treated with trastuzumab deruxtecan had a median progression-free survival (PFS) of 13.2 compared with those who were randomized to chemotherapy with a PFS of 8.1 months. Furthermore, patients treated with trastuzumab deruxtecan had a confirmed overall response rate (ORR) of 62.6%, compared with 34.4% for chemotherapy. In an important finding garnered through an exploratory analysis, these results were found to be consistent between patients expressing HER2-low and HER2-ultralow.1,2
Trial Name: Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)
ClinicalTrials.gov ID: NCT04494425
Sponsor: AstraZeneca
Estimated Completion Date: June 19, 2026
Study investigators also reported adverse events (AEs); AEs considered grade 3 or higher were observed in 52.8% of patients receiving trastuzumab deruxtecan, while they occurred in 44.4% of those receiving chemotherapy. Serious AEs of adjudicated interstitial lung disease or pneumonitis were observed in 49 patients. However, the investigators determined that the safety profile of trastuzumab deruxtecan was consistent with previously reported clinical trial results, with no novel concerns observed.1,2
The new indication for trastuzumab deruxtecan will allow for more patients to receive critical treatment for difficult-to-treat diseases for which therapeutic options are limited but steadily growing in number. Trastuzumab deruxtecan’s mechanism of action, consisting of a HER2 monoclonal antibody connected to multiple topoisomerase I inhibitor payloads, allows for more effective antitumor activity and faster response time. The drug combination is approved in dozens of countries for multiple other indications, including for patients with HER2+ breast cancer.1,2
“We are excited to see more treatment options for these patients which enable more personalized care. It is critical for patients to understand the HER2 status of their metastatic breast cancer to help them make informed treatment decisions,” Krissa Smith, vice president, education at Susan G Komen, said in the news release. "Patients with tumours that are HER2-low or HER2-ultralow now have more options to consider with their healthcare team.”1
