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

Abstract

Abstract Background Real-world comparative data on the safety of adjuvant trastuzumab emtansine (T-DM1) vs 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 4 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 > .05 for all comparisons). T-DM1 was associated with higher rates of thrombocytopenia (70% vs 36.1%, P < .001), ALT elevation (20% vs 4.8%, P = .008), AST elevation (24.5% vs 2.4%, P < .001), and early pulmonary toxicity (48.8% vs 24.1%, P = .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 = .001), ALT elevation (adjusted OR = 4.12, P = .026), and early pulmonary toxicity (adjusted OR = 2.64, P = .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.