Dr Lenz on the Prognostic Value of HER2 Expression in mCRC

Heinz-Josef Lenz, MD, FACP, associate director, Clinical Research, chair, Gastrointestinal (GI) Oncology Program, co-director, Colorectal Center, University of Southern California (USC) Norris Comprehensive Cancer Center; professor, Department of Medicine, Department of Preventive Medicine, Division of Oncology, Keck School of Medicine, discusses the prognostic value of HER2 expression in patients with KRAS wild-type metastatic colorectal cancer (CRC).

A study was designed to assess the potential prognostic and predictive implications of HER2 amplification and gene expression using next-generation sequencing (NGS) and NanoString analysis of select patients enrolled in the phase 3 CALGB/SWOG-80405 trial (NCT00265850).

Findings revealed that patients exhibiting high levels of HER2 expression experienced significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with those with low HER2 expression, irrespective of their treatment regimen, Lenz reports. The median PFS was 11.6 months for the high-HER2 group vs 10 months for the low-HER2 group (P = .012), with a corresponding median OS duration of 32 months and 25.3 months, respectively (P = .033), he details.

Furthermore, high HER2 expression was correlated with extended OS (HR, 0.83; 95% CI, 0.75-0.93; adjusted P = .0007) and PFS (HR, 0.82; 95% CI, 0.74-0.91; adjusted P = .0002), which plateaued after reaching the median, Lenz adds.

The analysis also revealed differential treatment outcomes with cetuximab (Erbitux)– vs bevacizumab (Avastin)-based therapy according to HER2 expression levels, Lenz says. In the subset of patients with high HER2 expression, treatment with the cetuximab regimen was associated with improved OS vs bevacizumab (P = .02); in the low-expression group, cetuximab was associated with lower PFS compared with bevacizumab (P = .019). Conversely, patients with lower HER2 expression exhibited poorer PFS (HR, 1.38; 95% CI 1.12-1.71; adjusted P = .0027) and OS (HR,1.28; 95% CI 1.02- 1.59; adjusted P = .03) when treated with cetuximab vs bevacizumab.

These findings were contrary to investigators' expectation that higher HER2 levels would be associated with cetuximab resistance, Lenz notes. Overall, these data underscore the prognostic value of HER2 expression in determining treatment response and outcomes in patients with metastatic CRC, he concludes.