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

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Abstract Background Despite the established benefit of adjuvant trastuzumab emtansine (T-DM1) over trastuzumab in HER2-positive early breast cancer (eBC) with residual disease after neoadjuvant chemotherapy plus HER2-targeted therapy, comparison of efficacy between T-DM1 and dual HER2 blockade (trastuzumab plus pertuzumab, HP) remains undetermined. This study evaluates survival outcomes with adjuvant T-DM1 versus HP in a multicenter real-world cohort. Methods Breast cancer patients with residual disease after neoadjuvant treatment from 3 centers in China who received either T-DM1 or HP from 2018 to 2024 were included. To analyze treatment effects, multivariable Cox regression was utilized as the primary analysis, with sensitivity analyses employing Firth’s penalized method, inverse probability of treatment weighting (IPTW), and propensity score matching (PSM) in the anthracycline (AC)-naïve cohort ( N = 212). Results Totally 230 patients were enrolled. Among them, 203 received TCbHP, 9 received THP, and 18 received AC-containing chemotherapy plus HP before surgery. In the AC-naïve cohort, 89 had T-DM1 as adjuvant treatment and 123 had HP instead. More iDFS events were observed in HP group than T-DM1 group (19 vs. 2 events respectively). Multivariable Cox regression demonstrated superior iDFS with T-DM1 compared with HP (2-year iDFS: 97.6% vs. 89.5%; 3-year iDFS: 97.6% vs. 82.9%; HR = 0.17, 95% CI 0.04–0.75, p = 0.020). Consistent survival benefits in the T-DM1 group were validated across sensitivity analyses using Firth’s penalized method, IPTW, and PSM. Conclusions Adjuvant T-DM1 was associated with improved early iDFS compared with HP in HER2 + eBC patients with residual disease following neoadjuvant chemotherapy combined with HER2-targeted therapy.