Trastuzumab deruxtecan, an antibody-drug conjugate, showed “promising and durable activity” in HER2-positive metastatic colorectal cancer (CRC) refractory to standard treatment in an open-label phase-2 trial.
HER2 amplification is seen in 2% to 3% of colorectal tumors, but there are currently no approved HER2-targeted therapies for colorectal cancer.
The DESTINY-CRC01 trial evaluated trastuzumab deruxtecan in 78 patients with HER2-expressing metastatic CRC that had progressed on two or more previous regimens, including HER2-targeted therapies other than trastuzumab deruxtecan.
Patients were grouped by HER2-expression level: cohort A (HER2-positive, immunohistochemistry (IHC) 3+ or IHC2+ and in-situ hybridization (ISH)-positive; 53 patients); cohort B (IHC2+ and ISH-negative, seven patients); cohort C (IHC1+, 18 patients).
They received 6.4 mg/kg trastuzumab deruxtecan intravenously every three weeks until disease progression, unacceptable side effects, withdrawal of consent, or death.
After median follow up of 27 weeks, the objective response rate in cohort A (the primary endpoint) was 45.3% (24 of 53 patients). There was one (2%) complete response (2%) and 23 partial responses (43%), Dr. Salvatore Siena of the University of Milan, in Italy, and colleagues report in The Lancet Oncology.
Within cohort A, a greater proportion of patients with high levels of HER2 expression (IHC3+) had an objective response than did patients with IHC2+ and ISH-positive tumors (57.5% vs. 7.7%). “However, due to the low number of patients enrolled with IHC2+ and ISH-positive tumors, further studies are needed,” the investigators say.
“Although trastuzumab deruxtecan has shown antitumour activity in HER2-low breast tumors, no responses were seen among patients with HER2-low metastatic colorectal cancer tumors (cohort B, IHC2+ and ISH-negative; cohort C, IHC1+),” they note.
Source: Medscape