Impact of PIK3CA and cell cycle pathway alterations on durvalumab efficacy in head and neck squamous cell carcinoma

초록

Background It is unknown whether genetic alterations in PIK3CA and the cell cycle pathway influence the efficacy of immune checkpoint inhibitors (ICI) in head and neck squamous cell carcinoma (HNSCC). We evaluated the effectiveness of durvalumab in patients with HNSCC based on genetic alterations. Methods We obtained data from phase II umbrella trial (TRIUMPH, NCT03292250) for HNSCC patients who had failed platinum-based therapy. Patients assigned to durvalumab included those with PIK3CA mutation (group A), those with cell cycle pathway mutations such as CDKN2A (group B) and those without druggable genetic mutations (group C). We analyzed the overall response rate (ORR), progression-free survival (PFS) of durvalumab and overall survival (OS) in each group, as well as potential predictive factors for durvalumab. Results A total of 87 patients were analyzed: 18 in group A, 12 in group B, and 57 in group C. In groups A, B, C, the ORRs was 27.8%, 8.3% and 15.8%, respectively (P=0.329). The median PFS was 2.3, 1.6, and 1.7 months, (P=0.24), and the median OS was 12.7, 11.2, and 14.9 months, respectively (P=0.72). Baseline neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were associated with a longer PFS (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.25-0.67, P<0.001; low PLR: HR 0.29, 95% CI 0.14-0.6, P=0.001). Low PFS and PLR were also associated with a longer OS (low NLR: HR 0.44, 95% CI 0.25-0.77, P=0.005; low PLR: HR 0.31, 95% CI 0.15-0.68, P=0.003). Conclusions In platinum refractory HNSCC, the efficacy of durvalumab is comparable regardless of the presence of PIK3CA or cell cycle pathway genetic alterations. Genetic alterations in PIK3CA or the cell cycle pathway have no effect on ICI outcomes. NLR and PLR could be predictive biomarkers with potential.