Molecular Alterations and Buparlisib Efficacy in Patients with Squamous Cell Carcinoma of the Head and Neck: Biomarker Analysis from BERIL-1.

The preplanned exploratory analysis of the BERIL-1 trial presented here aimed to identify biomarkers of response to the combination of buparlisib and paclitaxel. BERIL-1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on/after one previous platinum-based chemotherapy regimen in the recurrent or metastatic setting were treated with either buparlisib plus paclitaxel or placebo plus paclitaxel. Archival tumor tissue and ctDNA samples were analyzed for molecular alterations and immune infiltration using next-generation sequencing or immunohistochemistry. Biomarker analyses were performed in randomized patients ( = 158) with available biomarker data. The most frequently (>5%) mutated genes were , and Patients with SCCHN tumors (from various primary sites) having HPV-negative status (HR = 0.51), alterations (HR = 0.55) or low mutational load (HR = 0.57) derived overall survival (OS) benefit with the combination of buparlisib and paclitaxel. OS benefit with this combination was also increased in patients with presence of intratumoral TILs ≥10% (HR = 0.51), stromal TILs ≥15% (HR = 0.53), intratumoral CD8-positive cells ≥5% (HR = 0.45), stromal CD8-positive cells ≥10% (HR = 0.47), or CD8-positive cells in invasive margins >25% (HR = 0.37). A trend for improved progression-free survival with the combination of buparlisib and paclitaxel was also observed in these patients. The BERIL-1 biomarker analyses showed that patients with alterations, HPV-negative status, low mutational load, or high infiltration of TILs or CD8-positive cells derived survival benefit with the combination of buparlisib and paclitaxel. .