- The antibody-drug conjugate trastuzumab plus the cytotoxic agent emtansine (T-DM1) prolongs invasive DFS by 50% vs trastuzumab alone in patients with HER2+ early breast cancer with residual invasive disease after receipt of neoadjuvant chemotherapy (NACT) containing a taxane (±anthracycline) and trastuzumab before surgery.
Why this matters
- Patients with residual breast cancer have worse prognosis than those without.
- Randomized controlled phase 3 KATHERINE trial (n=1486) comparing T-DM1 (3.6 mg/kg) vs trastuzumab (6 mg/kg) for 14 cycles in patients with residual invasive disease in the breast or axilla at surgery after receipt of NACT+trastuzumab.
- Primary outcome: invasive DFS (freedom from recurrence or death from any cause).
- Funding: F. Hoffmann-LaRoche/Genentech.
- At interim analysis (after ~67% of invasive disease events), T-DM1 was associated with a lower rate of invasive disease or death vs trastuzumab (12.2% vs 22.2%).
- Invasive DFS was 50% longer with T-DM1 (HR, 0.50; P<.001>
- T-DM1 yielded a lower rate of distant recurrence as the first invasive-disease event (10.5% vs 15.9%).
- No new safety signals emerged; T-DM1 yielded a higher rate of adverse events (98.8% vs 93.3%).
- Loss of HER2+ status may have occurred but was unmeasured.