A recent study demonstrated that trastuzumab emtansine could improve both invasive disease–free survival and overall survival compared with trastuzumab alone in patients with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant therapy.

In the study, published in the The New England Journal of Medicine, researchers reported that trastuzumab emtansine (T-DM1) reduced the risk of invasive disease recurrence or mortality by 46% (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.44–0.66).

After a median follow-up of 8.4 years, the researchers found that the 7-year invasive disease–free survival (IDFS) rate was 80.8% in the T-DM1 group compared with 67.1% in the trastuzumab alone group—a 13.7 percentage–point difference. Additionally, T-DM1 was associated with a 34% lower risk of mortality (HR = 0.66, 95% CI = 0.51–0.87, P = .003). The 7-year overall survival (OS) rate was 89.1% in the T-DM1 group vs 84.4% in the trastuzumab alone group, representing a 4.7 percentage–point improvement.

Further, T-DM1 sustained the improvement in IDFS over trastuzumab alone (unstratified HR for invasive disease or mortality = 0.54, 95% CI = 0.44–0.66), emphasized lead study author Charles E. Geyer, Jr, MD, of the UPMC Hillman Cancer Center, and his colleagues. 

The KATHERINE trial, a phase III, open-label study, enrolled 1,486 patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axilla following neoadjuvant systemic therapy, which included taxane-based chemotherapy and trastuzumab. The participants were randomly assigned to receive 14 cycles of either T-DM1 or trastuzumab alone as adjuvant therapy.

Meanwhile, grade 3 or higher adverse events (AE) were more frequently observed in the T-DM1 group (26.1%) compared with the trastuzumab alone group (15.7%). The most common grade 3 or higher AEs in the T-DM1 group included thrombocytopenia and elevated liver enzyme levels.

Despite the higher rate of adverse events, T-DM1 demonstrated a significant clinical benefit in reducing the risk of cancer recurrence and mortality in this high-risk patient population.

The study highlighted T-DM1 as a treatment option among patients with HER2-positive early breast cancer who did not achieve a complete response following neoadjuvant therapy. Patients with residual invasive disease remained at high risk for cancer recurrence, but T-DM1 represented an effective intervention to reduce that risk.

The KATHERINE trial confirmed T-DM1’s role in improving long-term outcomes among patients with HER2-positive early breast cancer and residual invasive disease. The findings reinforced the importance of tailoring adjuvant therapy to address recurrence risk in this population.

The trial was funded by F. Hoffmann–La Roche/Genentech, the developer of T-DM1. Disclosures from study authors included financial relationships with Roche/Genentech and other pharmaceutical companies.