Hengrui's Trastuzumab Rezetecan Boosts Progression-Free Survival in Chemotherapy-Refractory Cancer
核心洞察
Phase III HORIZON-CRC-01 showed median progression-free survival of 5.5 months with trastuzumab rezetecan versus 2.8 months with standard of care in chemotherapy-refractory HER2 (搜索)-positive advanced colorectal cancer (搜索).
Objective response rate by independent review was 40.7% with the HER2 (搜索)-directed antibody-drug conjugate versus 4.5% with investigator's choice of TAS-102, fruquintinib or regorafenib.
Overall survival data remain immature with a hazard ratio of 0.77, and grade 3 or higher treatment-related adverse events occurred in 48.8% of trastuzumab rezetecan patients versus 50.0% on standard of care.
The HER2 (搜索)-directed antibody-drug conjugate trastuzumab rezetecan significantly improved progression-free survival and produced higher response rates than standard of care in patients with chemotherapy-refractory, HER2-positive, RAS/RAF wild-type advanced colorectal cancer (搜索), according to phase III HORIZON-CRC-01 results presented at the 2026 ASCO Annual Meeting.
At a median follow-up of 9.6 months, median progression-free survival by independent review was 5.5 months with trastuzumab rezetecan versus 2.8 months with standard of care (HR = 0.33; P < .0001), a 67% reduction in the risk of disease progression or death. Investigator-assessed progression-free survival was 5.6 versus 2.8 months (HR = 0.31; P < .0001). Objective response rate by independent review was 40.7% versus 4.5%, and median duration of response was 4.4 versus 3.4 months. Overall survival data were immature, with median overall survival not reached in either arm; the hazard ratio numerically favored trastuzumab rezetecan (HR = 0.77, 95% CI = 0.35-1.73).
The randomized, open-label, multicenter trial enrolled patients whose disease progressed after standard second-line therapy, randomly assigning them 2:1 to trastuzumab rezetecan 4.8 mg/kg intravenously every 3 weeks or investigator's choice of TAS-102, fruquintinib or regorafenib. As of the October 31, 2025, data cutoff, 130 patients were randomized, 86 to trastuzumab rezetecan and 44 to standard of care; 70.8% had HER2 (搜索) immunohistochemistry 3+ disease. Treatment-related adverse events occurred in 98.8% and 97.7% of patients, respectively, with grade 3 or higher events in 48.8% versus 50.0%. No patients discontinued treatment because of treatment-related adverse events. Myelosuppression, including neutropenia, thrombocytopenia and anemia, was the most common toxicity with trastuzumab rezetecan, and two treatment-related deaths occurred in that arm, one from septic shock and one from myelosuppression. The discussant noted limitations including immature overall survival, absent quality-of-life data, myelosuppression-related toxicity and questions about generalizability outside China. The study was funded by Jiangsu Hengrui Pharmaceuticals (搜索).