Multi-institutional Analysis of Next Generation Sequencing of Cell Free Circulating Tumor DNA of Blood Samples from Recurrent and Metastatic Head and Neck Cancer Patients

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an increasingly prevalent disease but effective targeted therapy is lacking. The use of next-generation sequencing (NGS) in the identification of novel targets has been suggested as a way to potentially expand therapeutic options and thereby improve outcomes. We designed a retrospective study to further characterize the results of blood sample sequencing in recurrent and metastatic (R/M) head and neck cancer (HNC) patients, to determine its ability to identify actionable mutations, and also to further elucidate the utility of liquid biopsies and its role in patient management. Using Guardant360, a 70-gene circulating tumor DNA (ctDNA) NGS platform, molecular profiling of blood samples was obtained from patients with recurrent and metastatic (R/M) head and neck cancers. ctDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST. Eighty-eight HNSCC patients were evaluated from February 2015 to February 2017. The most common tumor type and histology was oropharyngeal squamous cell carcinoma (n=23), which was commonly human papillomavirus (HPV) positive (n=17). Other cancer types included nasopharyngeal, salivary gland, and thyroid cancers. The most common mutations identified by ctDNA analysis were TP53 (51%) PIK3CA (25%), NOTCH1 (14.8%), and ARID1A (14.8%). Of the 29 matched tumor samples, TP53 (48%) and PIK3CA (24%) were also reported with the highest frequency. Eighty-seven percent of HNSCC, 67% of NPC, 75% of thyroid, and 63% salivary gland cancer patients had actionable mutations. Among these, 10.2% (n=9) received matched targeted therapy (MTT): 1 (11%) had partial response (PR), 5 (56%) had stable disease (SD), and 3 (33%) had progressive disease (PD). Thirty-six (40.9%) patients received immunotherapy: 1 (2.8%) had complete response, 3 (8.3%) had partial response, 15 (41.7%) had stable disease, 16 (44.4%) had progressive disease, and 1 patient is not yet evaluable. Alterations identified by ctDNA may help inform management decisions in R/M HNSCC. The majority of patients had unique mutations identified on ctDNA. TP53 and PIK3CA mutations were seen at the highest frequency in both ctDNA and matched tumor samples. The utility of ctDNA NGS and its role in patient management should be explored in future studies.