A chemotherapy drug that targets tumors has demonstrated remarkable effectiveness against some of the most difficult cancer cells to treat—specifically, those that have metastasized to the brain in individuals with advanced HER2-positive breast cancer. Research from an international clinical trial, led by experts at Dana-Farber Cancer Institute, underscores previous findings that highlight the advantages of this drug—trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate—for these patients, according to trial leaders.
The outcomes of this trial, known as the DESTINY-Breast12 study, were shared today at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain, and were published simultaneously in the journal Nature Medicine.
Researchers view these findings as indicative of T-DXd being a promising new treatment avenue for patients battling a particularly aggressive type of cancer. “Nearly half of patients with HER2-positive breast cancer experience brain metastases, which generally has a worse prognosis compared to breast cancer that hasn’t spread to the brain,” explains Nancy Lin, MD, the trial leader and senior author of the Nature Medicine study. Lin is the associate chief of the Division of Breast Oncology at Dana-Farber, affiliated with the Susan F. Smith Center for Women’s Cancers, and heads the Metastatic Breast Cancer Program. Methods such as surgery, radiosurgery, and radiation therapy are typically employed to manage brain metastases, yet progression in the central nervous system—the brain and spinal cord—commonly occurs within six to twelve months post-treatment.
Trastuzumab deruxtecan combines the chemotherapy agent deruxtecan with an antibody designed to target the HER2 protein found on breast cancer cells. While trastuzumab is a cornerstone therapy for HER2-positive breast cancer that has metastasized to various body parts—including the brain—patients receiving this treatment often see their condition advance, particularly in the central nervous system.
“There is an urgent need for additional systemic therapies for patients with brain metastases,” Lin notes.
The DESTINY-Breast12 trial included 504 patients with HER2-positive breast cancer treated across 78 cancer centers located in Western Europe, Japan, Australia, and the United States. Among the participants, 263 had active or stable brain metastases, while 241 had none. All participants had undergone at least one treatment prior to joining the trial.
After a median follow-up period of 15.4 months, researchers determined that participants with brain metastases experienced a median progression-free survival of 17.3 months—indicating how long patients lived with cancer before it worsened. Furthermore, the 12-month progression-free survival rate stood at 61.6%. Impressively, 71% of the participants showed an intracranial objective response—a quantifiable reduction of their cancer within the central nervous system. As anticipated, there was also a high response rate for tumors outside the central nervous system among individuals with or without brain metastases. Ninety percent of patients from both groups remained alive one year after initiating T-DXd treatment.
The side effects linked to T-DXd aligned with those observed in previous studies, including nausea, constipation, neutropenia (decreased levels of a specific type of white blood cell), fatigue, and anemia. Interstitial lung disease (ILD), a recognized risk associated with T-DXd, was noted at rates similar to previous studies, and careful monitoring for this potentially life-threatening side effect is crucial.
“Our findings indicate that T-DXd exhibits significant and long-lasting activity in the brains of patients with HER2-positive breast cancer that has spread there,” Lin says. “These results affirm the continued use of this drug in treating this patient demographic.”
