RTOG 0522: The KRAS Variant and Response to Cetuximab
In many cancers, KRAS mutations can predict cancer risk, unique cancer biology, and response to certain therapeutic agents. RTOG 0522 was a phase 3 trial of cisplatin/radiation ± cetuximab for patients with locally advanced SCCHN, evaluating whether KRAS mutation status would predict the response to cetuximab in these patients (Weidhaas JB, et al. ASCO 2014. Abstract 6000). There were 413 eligible patients on RTG 0522 for whom tissue for KRAS testing was available; 70 of these patients (16.9%) were KRAS+. At 12 months, progression-free survival (PFS) was significantly higher in the KRAS-variant group who had received cetuximab (hazard ratio, 0.31; P = .04), but not in the KRAS–wild-type (wt) group. Overall survival (OS) was also significantly improved in the KRAS-mutant group receiving cetuximab compared with the KRAS-wt group. These data suggest that there is a significant benefit in adding cetuximab to chemoradiotherapy for KRAS-mutant patients with locally advanced SCCHN, resulting in improved PFS and OS.