Research report: Adjuvant T-DM1 versus trastuzumab plus pertuzumab for residual disease after neoadjuvant dual HER2 blockade in HER2-positive early breast cancer: a multicenter real-world study

In a multicenter real-world cohort from China, adjuvant trastuzumab emtansine (T-DM1) was associated with longer invasive disease-free survival than trastuzumab plus pertuzumab (HP) among patients with HER2-positive early breast cancer who had residual disease after neoadjuvant chemotherapy and HER2-targeted therapy. The analysis included 230 patients treated at three centers between 2018 and 2024. In the primary anthracycline-naïve cohort of 212 patients, 89 received T-DM1 and 123 received HP.

During follow-up, invasive disease-free survival events occurred in two patients in the T-DM1 group and 19 in the HP group. Multivariable Cox regression estimated a hazard ratio of 0.17 for T-DM1 relative to HP, with a 95% confidence interval of 0.04–0.75 and a p-value of 0.020. Estimated invasive disease-free survival was 97.6% with T-DM1 and 89.5% with HP at two years; at three years, the estimates were 97.6% and 82.9%, respectively.

The study addressed a treatment-choice question involving patients with residual disease after neoadjuvant treatment. T-DM1 had an established benefit over trastuzumab in this setting, but comparative evidence for T-DM1 versus continued dual HER2 blockade with HP was undetermined. The investigators examined whether postoperative T-DM1 was associated with better early outcomes than postoperative HP.

The full cohort included 203 patients who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab, nine who received docetaxel, trastuzumab and pertuzumab, and 18 who received anthracycline- and cyclophosphamide-containing chemotherapy plus HP before surgery. The principal comparison was restricted to participants who had not received anthracycline-containing treatment, resulting in 212 patients in the analyzed cohort. Multivariable Cox regression was the primary analysis.

Sensitivity analyses used Firth’s penalized method, inverse probability of treatment weighting and propensity score matching. All three approaches produced results consistent with the primary model and favored adjuvant T-DM1 over HP. T-DM1 was associated with fewer events and a lower estimated event hazard than HP, with the largest separation appearing in the two- and three-year survival estimates.

The event count was also small, particularly in the T-DM1 group, and the 95% confidence interval for the hazard ratio ranged from 0.04 to 0.75, indicating uncertainty around the size of the association. These results are observational and apply to the population studied: patients with HER2-positive early breast cancer and residual disease after neoadjuvant chemotherapy plus HER2-targeted treatment, treated at three Chinese centers. The findings show an association between postoperative treatment and early invasive disease-free survival rather than demonstrating that T-DM1 caused the difference.

Residual differences between the treatment groups cannot be completely excluded in a real-world cohort, even after adjustment and the sensitivity analyses. Overall, the study provides real-world evidence that adjuvant T-DM1 was associated with improved early invasive disease-free survival compared with HP in the analyzed population. The result was consistent across multivariable Cox regression, Firth’s penalized method, inverse probability of treatment weighting and propensity score matching.

Its interpretation is constrained by the small number of events in the T-DM1 group, the confidence interval around the estimated hazard ratio and the observational design.

Subject of Research: Real-world comparison of adjuvant T-DM1 and trastuzumab plus pertuzumab for residual HER2-positive early breast cancer

Article Title: Adjuvant T-DM1 versus trastuzumab plus pertuzumab for residual disease after neoadjuvant dual HER2 blockade in HER2-positive early breast cancer: a multicenter real-world study

Article References: Jia, Y., Liang, S., Wu, W., Han, Y., Peng, Z., Ji, D., Sang, D., Yang, M., Gao, J., Yu, B., Wang, J., Luo, Y., Lan, B., Chen, S., Zhang, P., Ma, F., Xu, B., & Fan, Y. (2026). Adjuvant T-DM1 versus trastuzumab plus pertuzumab for residual disease after neoadjuvant dual HER2 blockade in HER2-positive early breast cancer: a multicenter real-world study. BMC Cancer. https://doi.org/10.1186/s12885-026-16873-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16873-8

Keywords: HER2-positive breast cancer, trastuzumab emtansine, T-DM1, trastuzumab, pertuzumab, residual disease, neoadjuvant therapy, invasive disease-free survival, real-world cohort, comparative effectiveness, Adjuvant, versus