Trastuzumab emtansine (T-DM1) is an antibody-conjugated drug that showed the efficacy in patients with Her2-positive breast cancer. Trastuzumab deruxtecan (DS-8201a) is a novel antibody-conjugated drug that consists of one trastuzumab and eight deruxtecan, a topoisomerase I inhibitor. DS8-8201a have the potential of anti-tumor activity in trastuzumab emtansine-pretreated patients. A dose expansion phase I clinical trial enrolled 115 trastuzumab emtansine-pretreated patients with Her2-positive breast cancer. The hormone receptor status was positive in 70% (81/115) patients. 111 patients were evaluable for confirming best overall response. The response rate was 59.5% (66/111), and the disease control rate was 93.7% (104/111). The median progression-free survival was 22.1 months. The frequency of grade 3 or worse adverse events was 50% (57/115). The results revealed the efficacy and the manageable safety profile of DS-8201a in trastuzumab emtansine-pretreated patients.
Tamura K, et al. Lancet Oncol. 2019