Adjuvant Trastuzumab Emtansine Improves Invasive Disease-Free Survival in Patients with HER2+ Early Breast Cancer

Adjuvant trastuzumab emtansine (T-DM1, Kadcyla; Genentech) demonstrated improved overall survival (OS) and sustained improvement in invasive disease–free survival (IDFS) compared with trastuzumab (Herceptin; Genentech) alone in patients with human epidermal growth factor receptor 2–positive (HER2+) early breast cancer (EBC). The data, published in The New England Journal of Medicine, are from the phase 3 KATHERINE trial (NCT01772472).¹

Cancer cells | Image Credit: © pimmou - stock.adobe.com

HER2+ BC accounts for 20% of all BC diagnoses, totaling over 290,000 women in 2023 alone. It is a challenging disease to treat with a high risk of recurrence, especially for patients with residual invasive disease after neoadjuvant therapy. Novel HER2-targeted therapies, including T-DM1, have resulted in IDFS improvements of up to 85%, a stark increase from the average 35% IDFS in the 1980s.²

T-DM1 is a HER2-targeted antibody drug conjugate composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1. It received FDA approval in 2019 for the adjuvant treatment of patients with HER2+ EBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment, based on data from the randomized, multicenter, open-label phase 3 KATHERINE trial. In a primary analysis of the KATHERINE trial, T-DM1 improved OS and IDFS compared with trastuzumab alone.^2-4

In the trial, researchers evaluated the efficacy and safety of T-DM1 versus trastuzumab as adjuvant therapy for patients with HER2+ primary BC who have residual tumor present pathologically in the breast or axillary lymph nodes following preoperative therapy. The patients were randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. The primary end point was IDFS with a key secondary end point of OS.⁴

At the median follow-up of 8.4 years, patients treated with T-DM1 achieved sustained improvements in IDFS compared with trastuzumab (unstratified hazard ratio for invasive disease or death, 0.54; 95% confidence interval [CI], 0.44 to 0.66). Treatment with T-DMI resulted in a 7-year IDFS of 80.8% compared with 67.1% with trastuzumab (difference, 13.7 percentage points). The data also showed that T-DM1 was associated with a significantly lower risk of death than trastuzumab (unstratified hazard ratio, 0.66; 95% CI, 0.51 to 0.87; P=0.003). The 7-year OS was 89.1% with T-DM1 and 84.4% with trastuzumab (difference, 4.7 percentage points). The safety analysis revealed adverse events of grade 3 or higher were reported in 26.1% of the patients in the T-DM1 group and 15.7% of those in the trastuzumab group.⁴

These findings underscore the transformative potential of T-DM1 in HER2+ EBC by delivering sustained improvements in IDFS and OS. This advancement reinforces the critical role of novel HER2-targeted therapies in improving the standard of care, offering new hope for patients facing this challenging diagnosis.

REFERENCES

1. A study of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor in the breast or axillary lymph nodes following preoperative therapy (KATHERINE). Updated January 7, 2025. Accessed January 23, 2025. https://clinicaltrials.gov/study/NCT01772472

2. Paving the way for better outcomes in HER2+ early breast cancer treatment. Pharmacy Times. December 12, 2024. Accessed January 23, 2025. https://www.pharmacytimes.com/view/paving-the-way-for-better-outcomes-in-her2-early-breast-cancer-treatment

3. FDA approves ado-trastuzumab emtansine for early breast cancer. FDA. May 3, 2019. Accessed January 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ado-trastuzumab-emtansine-early-breast-cancer

4. Geyer C, Untuch M, Huang C, et al. Survival with trastuzumab emtansine in residual HER2-positive breast cancer. N J Engl Med. January 15, 2025. doi: 10.1056/NEJMoa2406070