Incorporation of next-generation sequencing into routine clinical care to direct treatment of head and neck squamous cell carcinoma.

Chau NG1, Li YY2, Jo VY3, Rabinowits G1, Lorch JH4, Tishler RB5, Margalit DN6, Schoenfeld JD5, Annino DJ7, Goguen L8, Thomas T9, Becker H2, Haddad T2,Krane JF10, Lindeman NI11, Shapiro GI2, Haddad RI12, Hammerman PS13.

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Abstract

PURPOSE:

The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes.

EXPERIMENTAL DESIGN:

Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient Head and Neck Oncology clinic between August 2011 to December 2014. We correlated tumor genomic profiling results with clinical outcomes.

RESULTS:

PI3K/RTK pathway activation occurred frequently (activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)). Alterations in pathways affecting cell cycle regulation (CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)), and squamous differentiation (NOTCH1 inactivation (8%), EP300 inactivation (6%)), were identified. PIK3CA amplification (n=43), not PIK3CA mutation, was associated with significantly poorer PFS (p= 0.0006). Oncogenic RAS mutations (n=13) were associated with significantly poorer PFS (p=0.0001) and lower OS (p=0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results and 50% achieved a partial response.

CONCLUSIONS:

Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort.