As reported in The New England Journal of Medicine by Geyer et al, interim analysis of overall survival in the phase III KATHERINE trial showed a significant benefit of ado-trastuzumab emtansine (T-DM1) vs trastuzumab in patients with residual invasive HER2-positive breast cancer after neoadjuvant systemic therapy.
The primary analysis of the trial showed that invasive disease–free survival was significantly better in the T-DM1 group.
Study Details
In the open-label international trial, 1,486 patients who had received neoadjuvant therapy with taxane-based chemotherapy and trastuzumab were randomly assigned to receive T-DM1 at 3.6 mg/kg (n = 743) or trastuzumab at 6 mg/kg (n = 743) every 3 weeks for 14 cycles. The current report provides the prespecified second interim analysis of overall survival and final analysis of invasive disease–free survival.
Key Findings
Median follow-up in both groups was approximately 8.4 years. The T-DM1 group exhibited significantly better overall survival vs the trastuzumab group (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.51–0.87, P = .003). Overall survival was 95.1% vs 84.4% at 3 years and 89.1% vs 84.4% at 7 years (absolute difference = 4.7% at 7 years).
The improvement in invasive disease–free survival was maintained in the T-DM1 group vs the trastuzumab group (HR = 0.54, 95% CI = 0.44–0.66). Invasive disease–free survival was 88.4% vs 77.1% at 3 years and 80.8% vs 67.1% at 7 years (absolute difference = 13.7% at 7 years).
At 7 years, disease-free survival was 79.4% vs 66.0% (HR = 0.57, 95% CI = 0.47–0.70) and distant recurrence–free survival was 84.5% vs 76.2% (HR = 0.60, 95% CI = 0.47–0.76).
During the trial period, treatment-related grade ≥ 3 adverse events occurred in 26.1% of the T-DM1 group vs 15.7% of the trastuzumab group. Serious adverse events occurred in 12.7% vs 8.1% of patients. Adverse events of any grade in the posttreatment period were observed in 3.2% vs 1.7% of patients.
The investigators concluded: “As compared with trastuzumab, T-DM1 improved overall survival with sustained improvement in invasive disease–free survival among patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy.”
Charles E. Geyer, Jr, MD, of UPMC Hillman Cancer Center, Pittsburgh, is the corresponding author for the New England Journal of Medicine article.
Disclosure: The study was funded by F. Hoffmann–La Roche/Genentech. For full disclosures of the study authors, visit nejm.org.
