As reported in the Journal of Clinical Oncology by Battaglin et al, an analysis from the phase III CALGB/SWOG 80405 trial of first-line chemotherapy plus bevacizumab or cetuximab in patients with metastatic colorectal cancer showed differences in outcomes according to HER2 gene–expression status.
Study Details
The trial found no difference in overall survival with bevacizumab vs cetuximab combined with chemotherapy. The current analysis involved primary tumor DNA from 559 patients profiled for HER2 amplification by next-generation sequencing using FoundationOne CDx and tumor tissue from 925 patients tested for NanoString gene expression using an 800-gene panel. Outcome measures were progression-free and overall survival according to HER2 expression.
Key Findings
High (median and above) vs low HER2 expression was associated with longer median progression-free survival (11.6 vs 10 months, P = .012) and median overall survival (32 vs 25.3 months, P = .033), independent of treatment with bevacizumab or cetuximab. Patients in the high-expression group treated with cetuximab showed longer median overall survival vs those treated with bevacizumab (35 vs 33.6 months, P = .02). Patients in the low-expression group treated with cetuximab had shorter median progression-free survival (9.2 vs 11 months, P = .020).
When HER2 expression was analyzed as a continuous variable, increased expression was associated with longer overall survival (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.75–0.93, P = .0007) and progression-free survival (HR = 0.82, 95% CI = 0.74–0.91, P = .0002) independent of treatment group, with a plateau after the median expression level. Among patients with HER2 expression lower than median, treatment with cetuximab was associated with worse progression-free survival (HR = 1.38, 95% CI = 1.12–1.71, P = .0027) and overall survival (HR = 1.28, 95% CI = 1.02–1.59, P = .03) vs treatment with bevacizumab.
Significant interactions between HER2 expression and treatment groups were observed for overall survival (P for interaction = .017), progression-free survival (P for interaction = .048), and objective response rate (P for interaction = .001).
The investigators concluded, “HER2 gene expression was prognostic and predictive in CALGB/SWOG 80405. HER2 tumor expression may inform treatment selection for patients with low HER2 favoring bevacizumab- vs cetuximab-based therapies.”
Heinz-Josef Lenz, MD, of the University of Southern California Norris Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and by Bristol Myers Squibb, Genentech, Pfizer, and Sanofi. For full disclosures of the study authors, visit ascopubs.org.
