Multicenter phase 3 trial of trastuzumab botidotin versus trastuzumab emtansine for HER2-positive advanced breast cancer

A phase 3 trial at 57 centers in China evaluated the safety and efficacy of the novel HER2-directed antibody-drug conjugate trastuzumab botidotin for the treatment of HER2-positive unresectable/metastatic breast cancer. Adult patients who had received prior trastuzumab and a taxane were randomized (1:1) to receive trastuzumab botidotin (n=182) or trastuzumab emtansine (n=183). The primary endpoint was progression-free survival (PFS), assessed by blinded independent central review. At data cutoff (median follow-up 14.9 months), the median PFS was 11.1 months in the trastuzumab botidotin group, as compared with 4.4 months in the trastuzumab emtansine group (HR 0.39; p<0.0001). Benefit was consistent among subgroups, including those defined by prior lines of anti-HER2 therapy, prior pertuzumab or anti-HER2 TKIs, and visceral metastases. The objective response rate was 76.9% (95% CI 70.1-82.2) with trastuzumab botidotin and 53.0% (45.5-60.4) with trastuzumab emtansine. Overall survival data were immature. Grade ≥ 3 treatment-related adverse events occurred in 69.8% and 63.7%, respectively. Ocular TRAEs had a high incidence with trastuzumab botidotin; however, most events generally recovered or resolved. Trastuzumab botidotin treatment had low incidences of pulmonary, hepatic, and GI toxicities. The authors conclude that among patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer PFS than trastuzumab emtansine, with a distinct safety profile.