Adding cetuximab to radiotherapy and cisplatin significantly improved PFS and OS in patients with KRAS-variant head and neck squamous cell carcinoma, according to a secondary analysis of a clinical trial.
“In HNSCC, the KRAS-variant is found in 15% to 32% of patients, and is, therefore, highly relevant,” Joanne B. Weidhaas, MD, PhD, professor of radiation oncology and director of the division of molecular and cellular oncology at University of California Los Angeles Health, and colleagues wrote. “To date, the role of altered immunity and TGF- β1 levels as potential mechanisms of cetuximab response in patients with the KRAS-variant has not been evaluated.”
Weidhaas and colleagues conducted a secondary analysis of a phase 3 trial of cisplatin plus radiotherapy with or without cetuximab. The study included 891 patients (88.2% male; 90.9% white), 413 of whom were sampled for the KRAS-variant. The researchers analyzed the correlations between KRAS-variant disease and outcome, p16 positivity and TGF- β1 levels.
Seventy patients (16.9%) had the KRAS-variant. Among these patients, cetuximab extended 1-year PFS (HR = 0.31; 95% CI, 0.10-0.94) and OS in years 1 to 2 (HR = 0.19; 95% CI, 0.04-0.86).
KRAS-variant patients who were p16 positive and were treated without cetuximab had a shorter PFS than those without the KRAS-variant (HR = 2.59; 95% CI, 0.91-7.33).
“There was a significant three-way interaction among the KRAS-variant, p16 status and treatment for OS,” Weidhaas and colleagues wrote. HR for KRAS-variant, cetuximab and p16-positive was 0.22 (95% CI, 0.03-1.66). HR for KRAS-variant, cetuximab and p16 negative was 1.43 (95% CI, 0.48-4.26). HR for KRAS-variant, no cetuximab and p16 positive was 2.48 (95% CI, 0.64-9.65). HR for KRAS-variant, no cetuximab and p16 negative was 0.61 (95% CI, 0.23-1.59).
“Although a germline biomarker that can identify individuals with altered immunity that can be used to direct the best therapeutic combinations is a bold new concept, the KRAS-variant is unfolding as a true candidate,” the researchers wrote. “On the basis of the findings in this study, defining how anticancer agents affecting the tumor–host–immune association differently affect patients with KRAS-variant is a critical and pressing need because this knowledge could help in personalizing developing immune-based cancer therapies for all patients.” – by Andy Polhamus
Disclosure: The researchers report no relevant financial disclosures.