Biomarker analysis of the E5397 phase III study suggested that the addition of cetuximab to cisplatin in R/M HNSCC improved PFS in PTEN high/PIK3CA wild type patients (representing the group with non-activation of PI3K pathway; P = 0.07) but not PTEN null/PIK3CA mutant patients (representing the group with activation of PI3K pathway; P = 0.6) [47]. This evidence concerns the gene PIK3CA and head and neck squamous cell carcinoma.