Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck
Mené sur 48 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade métastatique et/ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicitié du dacomitinib
Purpose: The goals of this study were to investigate the clinical activity, safety and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2 and HER4, in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by immunohistochemistry, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95% CI, 2.9-5.0) and 6.6 months (95% CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in PI3K-pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 v 4.9 months without mutations, P=0.013; 2.8 v 9.9 months with low expression, P=0.004). Those harboring PI3K-pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 v 12.5 months lacking PI3K-pathway mutations and with low inflammatory cytokine expression, P=0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K-pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.