p16(INK4a) status and survival benefit of EGFR inhibitors in head and neck squamous cell cancer: A systematic review and meta-analysis

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.