Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial
Mené sur 365 patientes atteintes d'un cancer du sein HER2+ de stade avancé (durée médiane de suivi : 14,9 mois), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du trastuzumab botidotin (un nouveau conjugué anticorps-médicament ciblant HER2) et du trastuzumab emtansine
Purpose: To evaluate the safety and efficacy of the novel human epidermal growth factor receptor 2 (HER2)–directed antibody-drug conjugate, trastuzumab botidotin, for the treatment of HER2-positive unresectable/metastatic breast cancer (BC).
Methods: In this phase III, open-label, multicenter trial (ClinicalTrials.gov identifier: NCT06968585), conducted at 57 centers in China, adult patients with HER2-positive, unresectable/metastatic BC who had received prior trastuzumab and a taxane were randomly assigned (1:1) to receive trastuzumab botidotin or trastuzumab emtansine. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR), using an intention-to-treat analysis. In a prespecified interim analysis of PFS per BICR, trastuzumab botidotin met the prespecified superiority boundary (P < .0001). We report here the prespecified final analysis of PFS.
Results: Between July 18, 2023, and April 26, 2024, 365 patients were randomly assigned to trastuzumab botidotin (n = 182) or trastuzumab emtansine (n = 183). At data cutoff (median follow-up, 14.9 months), trastuzumab botidotin resulted in longer PFS than trastuzumab emtansine (median, 11.1 v 4.4 months; hazard ratio [HR], 0.39 [95% CI, 0.30 to 0.51]; nominal P < .0001). Benefit was consistent across subgroups, including those defined by prior lines of anti-HER2 therapy, prior pertuzumab or anti-HER2 tyrosine kinase inhibitors, and visceral metastases. The objective response rate was 76.9% (95% CI, 70.1 to 82.8) with trastuzumab botidotin and 53.0% (95% CI, 45.5 to 60.4) with trastuzumab emtansine. Overall survival data were immature (medians not reached in either group; HR, 0.62 [95% CI, 0.38 to 1.03]). Grade ≥3 treatment-emergent adverse events occurred in 127 (69.8%) and 116 (63.7%) patients in each group, respectively. Ocular treatment-related adverse events had a high incidence with trastuzumab botidotin; however, with a protocol-defined algorithm, most events generally recovered or resolved. Trastuzumab botidotin treatment had low incidences of pulmonary, hematologic, hepatic, and GI toxicities.
Conclusion: Among patients with HER2-positive advanced BC previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer PFS than trastuzumab emtansine, with a distinct safety profile.
Journal of Clinical Oncology , résumé, 2026