SABCS 2018: KATHERINE Trial: Adjuvant Ado-Trastuzumab Emtansine vs Trastuzumab in Early-Stage HER2-Positive Breast Cancer
The phase III KATHERINE clinical trial compared the use of ado-trastuzumab emtansine (T-DM1; Kadcyla) vs trastuzumab (Herceptin) as adjuvant therapy in patients with HER2-positive early-stage breast cancer with residual invasive disease after receiving neoadjuvant chemotherapy and trastuzumab. The study showed that T-DM1 reduced the risk of developing an invasive recurrence or death by 50%. Secondary efficacy endpoints of disease-free survival and distant recurrence–free interval also demonstrated clinically meaningful improvements with T-DMI.
HER2-positive breast cancers account for approximately 15% to 20% of all newly diagnosed localized and metastatic invasive breast cancers. Patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy have a high risk of recurrence and death. The current standard of care for these patients is continuation of the same HER2-targeted therapy in the adjuvant setting for 1 year.
The study by Geyer et al was presented at the 2018 San Antonio Breast Cancer Symposium (Abstract GS1-10). The results were simulatenously published by von Minckwitz et al in The New England Journal of Medicine.
Study Details
The KATHERINE trial is a phase III, open-label, global study of 1,486 patients with HER2-positive early-stage breast cancer who received neoadjuvant chemotherapy, plus HER2-targeted therapy that included a taxane and trastuzumab, followed by surgery. All patients in the study had residual invasive disease in the breast or axillary lymph nodes.
Within 12 weeks of surgery, patients were randomly assigned 1:1 to T-DM1 (3.6 mg/kg intravenously [IV] every 3 weeks) or trastuzumab (6 mg/kg IV every 3 weeks) for 14 cycles. The primary endpoint was invasive disease–free survival.
The study found that with 256 invasive disease–free survival events reported, the administration of T-DM1 significantly improved invasive disease–free survival compared with trastuzumab (unstratified hazard ratio [HR] = 0.50; 95% confidence interval [CI] = 0.39–0.64). Invasive disease–free survival events occurred in 91 patients (12.2%) in the T-DM1 arm compared with 165 patients (22.2%) in the trastuzumab arm. A consistent benefit was shown across all stratification subgroups.
The overall survival analysis is immature at this point. The safety data were consistent with the known safety profile of T-DM1, with increases in adverse events associated with T-DM1 compared to trastuzumab alone.
“Adjuvant T-DM1 substantially improved [invasive disease–free survival] in patients with HER2-positive early-stage breast cancer with residual disease after completion of neoadjuvant therapy,” concluded the researchers.
Clinical Significance
“We found that T-DM1 reduced the risk of developing an invasive recurrence of the breast cancer or death by 50%, corresponding to an absolute improvement of 3-year invasive disease–free survival rate by 11.3 percentage points (77% with trastuzumab and 88.3% with T-DM1),” said Charles E. Geyer, Jr, MD, Professor of Medicine at Virginia Commonwealth University School of Medicine and lead author of this study, in a statement. “I believe these results will be practice-changing. The results should form the foundation of a new standard of care in patients with residual invasive breast cancer following neoadjuvant therapy. KATHERINE demonstrates that neoadjuvant therapy can be used to identify patients at increased risk for recurrence based on less than optimal response to standard neoadjuvant therapies who can benefit by switching to T-DM1.”
Disclosure: Funding for this study was provided by F. Hoffmann La Roche/Genentech. See the study authors’ full disclosures at sabcs.org.
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