P16(INK4a) status and survival benefit of EGFR inhibitors in head and neck squamous cell cancer: A systematic review and meta-analysis.

Abstract

We conducted a systematic review and meta-analysis to investigate the impact of p16(INK4a) status on survival benefits in head and neck squamous cell cancer (HNSCC) after anti-epidermal growth factor receptor (EGFR) based treatments. We identified studies assessing anti-EGFR based versus non-anti-EGFR based regimens in patients with unresectable locoregionally advanced, recurrent or metastatic HNSCC. The primary endpoint was progression-free survival (PFS). We assessed the risk of bias in each included study. Random-effects models were used to estimate the efficacy of anti-EGFR based treatments for the p16-positive/p16-negative patients and prespecified subgroups defined by treatment modalities (chemotherapy or radiotherapy). Ten studies with 1929 patients were included. Adding an EGFR inhibitor did not significantly improve PFS or overall survival (OS) in either p16-negative or p16-positive disease. Subgroup analyses suggested a significant PFS benefit (hazard ratio [HR] 0.58; P < 0.001) of adding an EGFR inhibitor to chemotherapy versus chemotherapy for p16-negative disease. The p16-negativity was also associated with a significant OS benefit (HR 0.77; P = 0.003) when studies with high risk of bias were excluded. In contrast, adding an EGFR inhibitor to chemotherapy provided no benefit in either PFS or OS for p16-positive disease. No benefit was shown in either PFS or OS from adding an EGFR inhibitor to radiotherapy or chemoradiotherapy versus chemoradiotherapy regardless of p16 status. For the first time, our meta-analysis provides evidence that efficacy of anti-EGFR based treatments could be dependent on both p16 status and treatment modality. p16 status is likely to have a role in predicting survival to anti-EGFR based treatments in recurrent or metastatic HNSCC.