For patients dealing with high-risk HER2-positive breast cancer, research from the phase 3 KATHERINE clinical trial indicates that post-surgery treatment with trastuzumab emtansine (T-DM1) significantly lessens the long-term chances of death or invasive disease by 46%, resulting in better survival rates compared to treatment with trastuzumab alone. This study was conducted by experts from the University of Pittsburgh and UPMC Hillman Cancer Center.
Today’s findings, shared in the New England Journal of Medicine (NEJM), offer compelling long-term data that T-DM1 serves as an effective treatment option for this specific group of breast cancer patients. This supports earlier conclusions from a 3-year follow-up published in NEJM in 2019, which reported that T-DM1 lowered the risk of death or invasive disease by 50%.
Lead author Dr. Charles E. Geyer Jr., a professor in the Division of Malignant Hematology and Medical Oncology at the Pitt School of Medicine, UPMC Hillman, and UPMC Magee-Womens Hospital, stated, “KATHERINE is a pivotal clinical trial that revealed T-DM1’s significantly enhanced effectiveness compared to trastuzumab, which led to the premature disclosure of the findings. These results have transformed the standard care for patients with HER2-positive early breast cancer worldwide. We continued monitoring the patients to fully comprehend the benefits, and our findings now demonstrate that T-DM1 achieves stable long-term improvements in invasive disease-free survival and overall survival.”
T-DM1 is an innovative treatment combining an antibody with a chemotherapy drug called emtansine. When trastuzumab binds to the HER2 receptor on cancer cells, it allows emtansine to penetrate the cancer cells more effectively and target them from within.
The KATHERINE trial encompassed 1,486 patients with HER2-positive early-stage breast cancer who were left with residual invasive disease in the breast or nearby lymph nodes after undergoing neoadjuvant treatment with taxane-based chemotherapy and trastuzumab, as well as subsequent surgical tumor removal. These individuals are at an elevated risk for recurrence and mortality.
Post-surgery, participants were randomly assigned to receive either the standard adjuvant trastuzumab or T-DM1.
After seven years, the invasive disease-free survival rate was 80.8% for those treated with T-DM1, compared to 67.1% for those receiving trastuzumab alone. Overall survival rates showed 89.1% for T-DM1 and 84.4% for trastuzumab.
While the T-DM1 group experienced more adverse events (26.1%) than those on trastuzumab (15.7%), the safety profile of T-DM1 was deemed acceptable overall.
Dr. Geyer noted that a significant aspect was the consistent benefit of T-DM1 across different patient demographics. The analysis highlighted roughly a 50% drop in the risk of death and invasive disease, independent of the disease’s severity at initial presentation, hormone receptor status, the type of neoadjuvant treatment, lymph node status at surgery, age, and race.
“In the beginning of my oncology career, we recognized that some breast cancers were more aggressive without knowing the reasons,” Dr. Geyer remarked. “The journey has come from discovering the HER2 gene amplification and its targeted overexpression as an oncogenic target, through the innovation of HER2 targeting therapies and conducting landmark trials. Being part of this HER2 development story has been immensely fulfilling, particularly as it leads us to establish a new standard of care for these patients.”
Yet, the narrative continues. Currently, Dr. Geyer and his team are exploring a promising new antibody-drug combination called trastuzumab deruxtecan, or T-DXd, aimed at specific patient groups, including those with lower HER2 expression, who didn’t respond as effectively to T-DM1 compared to those with high HER2 expression.
“As oncologists, our aspirations are high,” said Dr. Geyer. “We will not rest until we achieve 100% cancer-free survival rates for our breast cancer patients.”
Additional authors are acknowledged in the NEJM publication.
The KATHERINE clinical trial received funding from Hoffmann-La Roche/Genentech.
