The KRAS-Variant and Cetuximab Response in Head and Neck Squamous Cell Cancer: A Secondary Analysis of a Randomized Clinical Trial.

摘要: Importance There is a significant need to find biomarkers of response radiotherapy and cetuximab in locally advanced head neck squamous cell carcinoma (HNSCC) that predict altered immunity, thereby enabling personalized treatment. Objectives To examine whether the Kirsten rat sarcoma viral oncogene homolog ( KRAS ) – variant, germline mutation microRNA-binding site KRAS, predictive biomarker immunity setting cisplatin treatment evaluate interaction -variant with p16 status blood-based transforming growth factor β1 (TGF-β1). Design, Setting, Participants A total 891 patients HNSCC from phase 3 trial plus or without (NRG Oncology RTOG 0522) were included this study, 413 available samples genotyped for -variant. Genomic DNA was tested CLIA-certified laboratory. Correlation -variant, positivity, outcome, TGF-β1 levels evaluated. Hazard ratios (HRs) estimated Cox proportional hazards model. Main Outcomes Measures The correlation status, plasma tested. Results Of eligible protocol analyses (786 male [88.2%], 105 [11.2%] female, 810 white [90.9%], 81 nonwhite [9.1%]), had biological testing, 376 measurement. Seventy (16.9%) Overall, improved both progression-free survival (PFS) first year (HR, 0.31; 95% CI, 0.10-0.94; P  = .04) overall (OS) years 1 2 0.19; 0.04-0.86;  = .03). PFS treated cetuximab. p16-positive worse than 2.59; 0.91-7.33;  = .07). 3-way among OS positive, 0.22; 0.03-1.66; HR negative, 1.43; 0.48-4.26; no 2.48; 0.64-9.65; 0.61; 0.23-1.59;  = .02). Patients significantly elevated (median, 23 376.49 vs 18 476.52 pg/mL; = .03) treatment-related toxic effects. Conclusions Relevance KRAS- variant benefit addition cisplatin, there between status. Elevated suggests may help these by overcoming TGF-β1–induced suppression antitumor immunity. Trial Registration clinicaltrials.gov Identifier:NCT00265941