Adjuvant ado-trastuzumab emtansine (T-DM1) continued to improve invasive disease-free survival (IDFS) and overall survival (OS) versus adjuvant trastuzumab in patients with high-risk HER2-positive early breast cancer, according to 7-year follow-up of the phase 3 KATHERINE trial. All patients enrolled in the trial had residual invasive disease following neoadjuvant therapy. Updated results of KATHERINE were presented at the 2023 San Antonio Breast Cancer Symposium by lead study author, Sibylle Loibl, MD, PhD, Chief Executive Officer and Chair of the German Breast Group and Associate Professor of Obstetrics and Gynecology, Goethe University, Frankfurt, Germany.
At a median follow-up of 7 years, the absolute IDFS for T-DM1 was higher compared with trastuzumab, the former standard of care (80.8% vs 67.1%, respectively). In addition, T-DM1 led to improved OS compared to trastuzumab: 89.1% versus 84.4%, respectively. Key subgroups benefitted from T-DM1 versus trastuzumab, and rates of cardiotoxicity were low.
“TDM-1 is the first therapy to show a significant overall survival benefit in people with a high risk of recurrence due to residual invasive disease in the surgical specimen following neoadjuvant therapy for HER2-positive early breast cancer,” stated Dr Loibl.
At a press conference where these late-breaking data were discussed, moderator Virginia Kaklamani, MD, codirector of SABCS stated: “KATHERINE changed the standard of care when the data were first presented 5 years ago. We now treat patients with residual invasive disease following neoadjuvant chemotherapy with T-DM1, and we have better outcomes. Invasive disease-free survival is consistent with the original analysis. It is impressive that the curves remain separate after 7 years.”
KATHERINE was a prospective, randomized phase 3 trial that enrolled 1486 patients. All patients had HER2-positive early breast cancer treated with 6 cycles of chemotherapy and ≥9 weeks of trastuzumab as neoadjuvant therapy and residual invasive tumor in the breast and nodes after surgery. A second HER2-targeted agent was also permitted. Baseline characteristics were well balanced between the 2 treatment arms.
Patients were randomized within 12 weeks of surgery in a 1:1 ratio to receive 14 cycles of either T-DM1 (n=740) or trastuzumab (n=720). Radiation and endocrine therapy were given at the investigator’s discretion, and crossover to trastuzumab was allowed for patients who experienced adverse events on T-DM1.
The rates of distant recurrence were 21.5% and 14.7% in the trastuzumab and T-DM1 arms, respectively, including central nervous system metastases in 5.1% and 7.0%, respectively. The rates of locoregional recurrence were 6.2% versus 2.2%, respectively. Contralateral breast cancer occurred in 2.6% versus 0.9%, respectively.
Breast cancer-specific cause of death occurred in 9.5% in the T-DM1 arm versus 15% in the trastuzumab arm. Deaths attributed to adverse events were reported in 0.1% versus none; other causes of death were reported in 2.4% versus 2.5%, respectively.
“Subgroup analysis underlined the treatment effect of T-DM1,” Dr Loibl stated. Patients with hormone receptor-positive and -negative disease, and those with minimal residual disease positive and negative, all had a benefit in IDFS.
No new safety signals emerged with longer follow-up from the KATHERINE trial. Any-grade adverse events were reported in 24 patients (3.2%) in the T-DM1 group and 12 patients (1.7%) in trastuzumab arm.
Serious adverse events occurred in 0.3% and 0.6% of patients in the T-DM1 and trastuzumab groups, respectively. (Cardiac toxicity, hepatobiliary toxicity, and vascular toxicity occurred in <1% of each arm.)
The KATHERINE study is sponsored by F. Hoffmann-La Roche Ltd.
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