Predictive and prognostic value of HER2 gene expression levels in patients with metastatic colorectal cancer in CALGB/SWOG 80405

The phase 3 CALGB/SWOG 80405 trial found no difference in overall survival in patients with metastatic colorectal cancer receiving first-lin chemotherapy plus either bevacizumab or cetuximab. A post-hoc analysis of the trial investigated the potential prognostic and predictive value of HER2 amplification and gene expression using next-generation sequencing and NanoString data. High HER2 expression (dichotomized at median) was associated with longer PFS (11.6 versus 10.0 months; p=0.012) and OS (32.0 versus 25.3 months; p=0.033), independent of treatment. An OS benefit for cetuximab versus bevacizumab was observed in the high HER2 expression group (p=0.02), whereas a worse PFS for cetuximab was seen in the low-expression group (p=0.019). The authors conclude that HER2 gene expression was prognostic and predictive in CALGB/SWOG 80405. HER2 tumor expression may inform treatment selection for patients with low HER2 expression favoring bevacizumab – versus cetuximab-based therapies.