Optimal Trastuzumab Deruxtecan Dose for Patients With HER2-Positive Metastatic Colorectal Cancer
According to final results from the phase 2 DESTINY-CRC02 trial, 5.4 mg/kg of trastuzumab deruxtecan (T-DXd) demonstrated preferable efficacy and safety compared to 6.4 mg/kg among patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic colorectal cancer (mCRC).
These data will be presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this study, 164 previously treated patients with HER2-positive, RAS wild-type or mutant mCRC received either 5.4 mg/kg (n = 82) or 6.4 mg/kg (n = 40) of T-DXd once every 3 weeks. The primary end point was the confirmed objective response rate (ORR). Key secondary end points included duration of response, overall survival (OS), and safety.
At analysis, the confirmed ORR was 37.8% in the 5.4 mg/kg arm and 27.5% in the 6.4 mg/kg arm. Median duration of response was 5.5 months in both treatment arms and median OS was 15.9 months and 19.7 months, respectively. Grade ≥3 drug-related treatment-emergent adverse events occurred in 42.2% of patients in the 5.4 mg/kg arm and 48.7% of patients in the 6.4 mg/kg arm. Adjudicated drug-related interstitial lung disease occurred in 9.6% and 17.9% of patients, respectively.
“The findings of this final analysis were consistent with the results of the primary analysis, supporting the efficacy of single-agent T-DXd 5.4 mg/kg in [patients] with [HER2-positive] mCRC with a more favorable benefit-risk profile,” concluded Dr Raghav et al.
Source:
Raghav K, Siena S, Takashima A, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic colorectal cancer (mCRC): Final analysis of DESTINY-CRC02, a randomized, phase II trial. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. 737MO
