New Trastuzumab Combo Therapy Shows Potential in HER2-Expressing Breast Cancers

Treatment with trastuzumab (Herceptin) duocarmazine, a novel human epidermal growth factor receptor (HER) 2-targeting antibody­–drug conjugate, demonstrated efficacy in patients with HER2-expressing metastatic breast cancer, according to a new study published in The Lancet Oncology.
The study represents an innovative approach of linking antibodies to specifically target cancer cells with chemotherapy drugs for patients who have developed resistance to other treatments, according to the researchers.
For the study, the researchers evaluated the 2-in-1 treatment in human patients for the first time in a phase 1 dose-escalation and dose-expansion clinical trial. The primary endpoint of the dose- escalation phase was to assess safety and ascertain the recommended phase 2 dose. The primary endpoint of the dose-expansion phase was the proportion of patients achieving an objective response.
Trastuzumab duocarmazine was administered intravenously on day 1 of each 3-week cycle. In the dose-escalation phase, the therapy was given at doses of 0.3 mg/kg to 2.4 mg/kg until disease progression or unacceptable toxicity, according to the study. A total of 39 patients were enrolled and treated in the dose-escalation phase and 146 patients were enrolled and treated in the dose-expansion phase.
In the dose-escalation phase, 1 dose-limiting toxic effect occurred at the highest administered dose and 1 further death occurred due to disease progression, according to the data. The most common treatment-related adverse effects were fatigue, conjunctivitis, and dry eye.
Based on the data, the recommended phase 2 dose was set at 1.2 mg/kg.
In the breast cancer dose-expansion cohorts, 33% of patients with HER2-positive breast cancer achieved an objective response, all partial responses, according to the study.
The treatment also showed efficacy in patients with lower levels of the HER2 protein. Twenty-eight percent of patients with HER2-low hormone receptor-positive breast cancer and 40% of patients with HER2-low hormone receptor-negative breast cancer achieved an objective response. Additionally, partial responses were also observed in 6% of patients with gastric cancer, 25% of patients with urothelial cancer, and 39% of patients with endometrial cancer.
Overall, patients with HER2-positive breast cancer lived for 7.6 months after starting treatment with no disease progression and those with lower HER2 levels had progression-free survival of 4.9 months.
There are currently no approved HER2-targeting therapies or antibody-drug conjugates for patients with low-HER2 breast cancer. A duocarmazine conjugate could be a potential therapeutic option for these patients in the future, the researchers said. Additionally, they noted that this approach may be extended to other cancer types with varying HER2 levels as well, as indicated by the responses seen in the study.
“Trastuzumab duocarmazine has shown promising anti-tumor activity in breast cancer patients with varying levels of the cancer-driving HER2 protein,” lead author Udai Banerji, MD, PhD, deputy director of the Drug Development Unit at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation, said in a statement. “As these cancers often develop resistance to the current standard of care, this treatment would extend the lives of patients who have otherwise run out of options.”
Banerji U, van Herpen C, Saura C, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-experssing breast cancer: a phase 1 dose-escalation and dose-expansion study. The Lancet Oncology. 2019. Doi:
Two-in-one drug combining Herceptin with chemotherapy keeps women’s breast cancers at bay [news release]. The Institute of Cancer Research. Accessed July 1, 2019.

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