A meta-analysis published in Current Oncology evaluated 6 clinical trials of HER2-targeted regimens for the treatment of HER2-positive metastatic colorectal cancer.
The treatments analyzed were:
- trastuzumab deruxtecan (2 trials)
- trastuzumab plus lapatinib (1 trial)
- pertuzumab plus trastuzumab emtansine (1 trial)
- trastuzumab plus tucatinib (1 trial)
- trastuzumab plus pyrotinib (1 trial)
The trials comprised 238 total patients. The pooled median number of prior lines of treatment was 3, ranging from 2 to 5 across all trials. The primary outcomes were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Secondary outcomes were adverse effects and safety.
The pooled ORR was 31.33% (95% CI, 24.27-38.39), and the pooled DCR was 74.37% (95% CI, 64.57-84.17). The pooled, weighted PFS was 6.2 months, suggesting “that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes.” The analysis showed that the regimen of trastuzumab deruxtecan was the most effective, achieving the highest DCR (>80%) and ORR.
Regarding safety, adverse effects were predictable and in line with what is seen with most chemotherapeutic agents. The most common adverse effects were grade 1-2 fatigue, nausea, vomiting, diarrhea, and dermatitis. Cytopenia, in particular thrombocytopenia, was common in regimens utilizing antibody-drug conjugates in the trials evaluating trastuzumab deruxtecan and pertuzumab plus trastuzumab emtansine.
The authors noted statistical heterogeneity in the ORR and DCR analyses, which “may be due to differences in study design, patient characteristics, or other factors not accounted for in this analysis.” They called for future research to understand the factors that impact variability in response to HER2-targeted therapies.
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