Multinational randomized phase 2 trial of trastuzumab deruxtecan for pretreated HER2-positive advanced colorectal cancer

The multinational randomized phase 2 DESTINY-CRC02 trial compared trastuzumab deruxtecan (T-DXd) 5.4 mg/kg versus 6.4 mg/kg every three weeks among patients with previously treated unresectable, recurrent of metastatic HER2-positive colorectal cancer. Confirmed objective response rate by blinded independent central review was 37.8% in the 5.4 mg/kg group and 27.5% in the 6.4 mg/kg group. Grade 3 or higher treatment-related adverse events occurred in 41% of patients in the 5.4 mg/mg group and 49% of patients in the 6.4 mg/kg group. One grade 5 TRAE occurred in the 5.4 mg/kg group (hepatic failure). Drug-related interstitial lung disease or pneumonitis was seen in 8% of patients in the 5.4 mg/kg group (all grade 1 or 2) and in 13% of patients in the 6.4 mg/kg group (one grade 5). The authors conclude that the promising antitumor activity and favorable safety profile support T-DXd 5.4 mg/kg every three weeks as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer.