Comparative safety of concurrent adjuvant trastuzumab emtansine versus trastuzumab with radiotherapy in HER2-positive early breast cancer.

BACKGROUND: Real-world comparative data on the safety of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab with concurrent radiotherapy (RT) in HER2-positive early breast cancer (BC) remain limited. METHODS: In this retrospective, multicenter study, we included 133 patients with HER2-positive early-stage BC treated with neoadjuvant therapy, surgery, and adjuvant systemic therapy administered concurrently with RT at four hospitals. Patients received adjuvant T-DM1 (n = 50) if residual disease was present, or trastuzumab (n = 83) if a pathologic complete response was achieved. Toxicities were graded according to CTCAE criteria. A post-hoc power analysis indicated 80% power to detect an absolute between-group difference in toxicity rates of ≥ 25%. RESULTS: The T-DM1 group had poorer performance status, higher nodal stage, and more intensive neoadjuvant regimens. RT parameters were balanced between groups (median dose 50 Gy, 25 fractions; p > 0.05 for all comparisons). T-DM1 was associated with higher rates of thrombocytopenia (70% versus 36.1%, p < 0.001), ALT elevation (20% versus 4.8%, p = 0.008), AST elevation (24.5% versus 2.4%, p < 0.001), and early pulmonary toxicity (48.8% versus 24.1%, p = 0.017), with events predominantly grade 1. In sensitivity analyses adjusting for pertuzumab exposure, T-DM1 associations remained significant for thrombocytopenia (adjusted odds ratio [OR] = 3.85, p = 0.001), ALT elevation (adjusted OR = 4.12, p = 0.026), and early pulmonary toxicity (adjusted OR = 2.64, p = 0.034). CONCLUSION: Concurrent adjuvant T-DM1 and RT demonstrated higher but manageable hematologic, hepatic, and pulmonary toxicity compared with trastuzumab. These hypothesis-generating findings require validation in prospective studies.