The evidence supporting this protocol is provided by the KATHERINE trial – a randomised, phase 3, open-label trial involving patients with HER2 positive early breast cancer who had received at least 9 weeks of neoadjuvant taxane-containing therapy (with or without anthracycline) and trastuzumab, and were subsequently found to have residual invasive disease in the breast or axilla at surgery.r
Between April 2013 and December 2015, 1486 women were randomised 1:1 to receive 14 cycles of adjuvant trastuzumab emtansine (T-DM1) at a dose of 3.6 mg/kg IV every 21 days, or 14 cycles of trastuzumab at a dose of 6 mg/kg IV every 21 days (with a loading dose of 8 mg/kg if there was a break of more than 6 weeks since the prior dose). 72.3% of patients were hormone receptor positive and 76.9% had received prior neoadjuvant anthracycline based therapy. Concurrent radiation therapy and/or endocrine therapy were permitted if indicated.
The primary end point was invasive disease-free survival (DFS). Secondary end points included DFS, overall survival (OS), distant recurrence–free survival, and safety.
After a median follow up of 41.4 months in the interim analysis, the use of T-DM1 demonstrated longer invasive DFS compared with trastuzumab (HR 0.50; 95% CI 0.39 to 0.64, P<0.001). Estimated DFS at 3 years was 88.3% in the T-DM1 group versus 77.0% in the trastuzumab group. TDM-1 also decreased the risk of distant recurrence (HR 0.60; 95% CI, 0.45 to 0.79).r
Kaplan-Meier curve of invasive disease-free survival (A), distant recurrence (B) and overall survival (C) in the interim analysisr
© N Engl J Med 2019
More patients reported grade 3 or above adverse events in the T-DM1 group (25.7%) compared with the trastuzumab group (15.4%). Of these, decreased platelet count (5.7% T-DM1 vs 0.3% trastuzumab) and hypertension (2% T-DM1 vs 1.2% trastuzumab) were the most common. Serious adverse events were higher in the T-DM1 (12.7%) group compared with the trastuzumab group (8.1%).r
© N Engl J Med 2019