An updated analysis of the Phase III KATHERINE trial demonstrates that adjuvant treatment with Kadcyla (trastuzumab emtansine; T-DM1) significantly improves overall survival (OS) and invasive disease-free survival (IDFS) compared to trastuzumab monotherapy in patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy. The findings, published in The New England Journal of Medicine, highlight the sustained benefits of T-DM1 across most patient subgroups with a manageable safety profile.
KATHERINE Trial Details
The KATHERINE trial (NCT01772472) was a randomized, multicenter, open-label study comparing the efficacy and safety of T-DM1 to trastuzumab monotherapy in the adjuvant setting. The trial enrolled patients with HER2-positive early breast cancer who had residual tumor in the breast or axillary lymph nodes following preoperative therapy. Patients were randomized 1:1 to receive either T-DM1 (3.6 mg/kg IV every three weeks) or trastuzumab monotherapy (6 mg/kg IV every three weeks) for 14 cycles.
Eligibility criteria included a minimum of six cycles of neoadjuvant chemotherapy with at least nine weeks of taxane-based therapy plus at least nine weeks of trastuzumab, and residual invasive cancer in the breast or resected axillary nodes at surgery. Randomization was stratified by clinical stage, hormone-receptor status, preoperative HER2-directed therapy, and pathological nodal status following neoadjuvant therapy.
Significant Survival Improvement
After a median follow-up of 8.4 years, T-DM1 demonstrated a sustained improvement in IDFS (unstratified hazard ratio for invasive disease or death, 0.54; 95% CI, 0.44 to 0.66), with a seven-year IDFS of 80.8% compared to 67.1% with trastuzumab monotherapy. The seven-year OS rate was 89.1% with T-DM1 compared to 84.4% with trastuzumab monotherapy (unstratified hazard ratio, 0.66; 95% CI, 0.51 to 0.87; P=0.003).
Safety Profile
Grade 3 or higher adverse events were reported in 26.1% of patients receiving T-DM1 compared to 15.7% of patients receiving trastuzumab monotherapy, indicating a manageable safety profile.
Clinical Impact
These long-term results from the KATHERINE trial provide further support for the use of adjuvant T-DM1 in patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy. The significant improvement in both IDFS and OS underscores the clinical benefit of T-DM1 in this high-risk patient population. As the study authors noted, "This prespecified long-term follow-up analysis provides additional support for the neoadjuvant therapy paradigm by showing that adjuvant T-DM1 also provided a significant improvement in overall survival and no evidence of long-term safety issues."
