According to final analysis and updated overall survival (OS) analysis of the phase 3 KATHERINE trial, trastuzumab emtansine significantly improved the overall survival among patients with residual invasive HER2-positive early breast cancer, following neoadjuvant chemotherapy and HER2-targeted therapy.

Sibylle Loibl, MD, PhD, German Breast Group, Neu-Isenburg, Germany, and coauthors wrote, “Patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy have a high risk of recurrence and death.”

These results were first presented at the 2023 San Antonio Breast Cancer Symposium.

The open label, global phase 3 KATHERINE trial enrolled patients with HER2-positive primary breast cancer who had received neoadjuvant chemotherapy and HER2-targeted therapy, including a taxane and trastuzumab, followed by surgery, with residual invasive disease in the breast and/or axillary nodes. Patients were randomized on a 1-to-1 basis to receive either trastuzumab emtansine or trastuzumab for 14 cycles. Patients received radiation and/or endocrine therapy as according to local standards. The primary end point was invasive disease-free survival (iDFS) Previously reported results from the primary analysis showed the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant ado-trastuzumab emtansine than with trastuzumab.

At a median follow-up duration of 8.4 years, the improvement in iDFS seen with trastuzumab emtansine over trastuzumab was sustained (unstratified hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.44 to 0.66; P < .0001). The 7-year iDFS rate was 67.1% in the trastuzumab arm compared with 80.8% in the trastuzumab emtansine arm. The risk of death was significant reduced, by 34% in the trastuzumab emtansine arm compared with the trastuzumab (unstratified HR, 0.66; 95% CI = 0.51 to 0.87; P = .0027). The 7-year OS rate was 84.4% with trastuzumab and 89.1% with trastuzumab emtansine. The benefit seen in both OS and iDFS with trastuzumab emtansine were observed across key subgroups. No new safety signals were observed, with cardiac toxicity being rare in either arm.

Dr Loibl et al concluded, “[Trastuzumab Emtansine is the first therapy to show improved survival post-surgery in patients with HER2-positive [early breast cancer] with residual invasive disease after neoadjuvant therapy.”

Source:

Loibl S, Mano MS, Untch M, et al. Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis. Presented at San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, Texas. Abstract GS03-12