Breakthrough cancer drug Enhertu (trastuzumab deruxtecan) appears to have scored another first, this time in a trial of metastatic breast cancer patients with HER2-low and HER2-ultralow tumors. Researchers also presented the first data supporting Enhertu as a first-line treatment in HER2-positive metastatic breast cancer.
Further, interim results from the DESTINY-Breast07 Phase Ib/II trial of Enhertu alone or in combination with other anticancer therapies as a 1st-line treatment for HER2-positive metastatic breast cancer demonstrated promising clinical activity for Enhertu as a monotherapy and or in combination with pertuzumab.
These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Enhertu is a HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized with AstraZeneca.
Early results from the DESTINY-Breast06 trial of HER2-positive patients showed Enhertu reduced the risk of disease progression or death by 38%. Median progression free survival (PFS) was 13.2 months in the Enhertu arm compared to 8.1 months for those on chemotherapy. In patients with HER2-ultralow expression, Enhertu reduced risk of disease progression or death by 22% compared to chemotherapy.
Initially approved in 2023, for the groundbreaking indication of HER2-low expression breast cancer, Enhertu also received solid tumor agnostic approval in April 2024. It’s now a blockbuster drug, with annual sales reportedly doubling from $1.238 billion to $2.556 billion.
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said, “Enhertu continues to deliver pioneering results for a HER2-directed medicine across many different types of cancer. These latest results from DESTINY-Breast06 demonstrate clinically meaningful results with Enhertu even in tumors with very low levels of HER2 expression, suggesting that it may have an important role in treating a wide range of HER2-expressing metastatic breast cancer.”
In the trial, HER2-low was defined as IHC 1+ or 2+/ISH, while HER2-ultralow was defined as IHC 0, following one or more lines of endocrine therapy.
Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milan and head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy and principal investigator for the trial, said, “Endocrine therapies are widely used early in the treatment of HR-positive metastatic breast cancer, but following one or more lines of treatment, patients often derive limited efficacy from further endocrine-based therapy. With a median progression-free survival of more than a year, the results from DESTINY-Breast06 show that Enhertu could become a new standard of care for patients with HER2-low- and HER2-ultralow-expressing tumors following endocrine therapy in the metastatic setting.”
In patients with HER2-low expression, confirmed objective response rate (ORR) was 56.5% for Enhertu versus 32.2% with chemotherapy. In the overall trial population, confirmed ORR was 57.3% for Enhertu versus 31.2% with chemotherapy and in patients with HER2-ultralow expression the confirmed ORR was 61.8% versus 26.3%, respectively. Complete responses were seen in 13 patients from the Enhertu arm, including nine patients with HER2-low expression. In the HER2-ultralow subgroup, four patients in the Enhertu arm had complete responses. No complete responses were seen in the chemotherapy arm.
Meanwhile, Interim results from the DESTINY-Breast07 Phase Ib/II trial of Enhertu alone or in combination with other anticancer therapies as a first-line treatment for HER2-positive metastatic breast cancer demonstrated promising clinical activity for Enhertu as a monotherapy (n=75) and in combination with pertuzumab (n=50).
There was a confirmed ORR of 76.0% with Enhertu and 84.0% with Enhertu in combination with pertuzumab. The 12-month PFS rate was 80.8% with Enhertu monotherapy and 89.4% with Enhertu and pertuzumab.
These are the first data presented for Enhertu as a first-line treatment in HER2-positive metastatic breast cancer.
