Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution

• Published in: PloS one Vol. 11; no. 4; p. e0154133
• Main Authors: Park, Hyung Soon, Lim, Sun Min, Kim, Sora, Kim, Sangwoo, Kim, Hye Ryun, Kwack, KyuBum, Lee, Min Goo, Kim, Joo-Hang, Moon, Yong Wha
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.04.2016; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adult; Afatinib; Aged; Antineoplastic Agents - therapeutic use; Asian Continental Ancestry Group - genetics; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Class I Phosphatidylinositol 3-Kinases; Clinical trials; Deoxyribonucleic acid; Diagnosis; DNA; DNA sequencing; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Drugs; Ear; Ear canal; ErbB-2 protein; Esophagus; Everolimus - therapeutic use; Feasibility Studies; Female; Genetic aspects; Genetic Predisposition to Disease - genetics; Genotype & phenotype; Genotypes; High-Throughput Nucleotide Sequencing - methods; Humans; Internal medicine; Kinases; Laboratories; Lung cancer; Male; Medical treatment; Medicine; Medicine and Health Sciences; Metastasis; Middle Aged; Molecular Targeted Therapy - methods; Multivariate analysis; Mutation; Neoplasms - drug therapy; Neoplasms - ethnology; Neoplasms - genetics; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Nucleotide sequence; Oncology; Paraffin; Patients; Phenylurea Compounds - therapeutic use; Phosphatidylinositol 3-Kinases - genetics; Pilot Projects; Precision Medicine - methods; Proto-Oncogene Proteins B-raf - genetics; Quinazolines - therapeutic use; Receptor, Platelet-Derived Growth Factor alpha - genetics; Republic of Korea; Science; Solid tumors; Sorafenib; Squamous cell carcinoma; Systematic review; Therapy; Tumors; Young Adult; South Korea; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154133

We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of available matched targeted agents. Formalin-fixed paraffin-embedded (FFPE) tumors were sequenced using the Comprehensive Cancer Panel (CCP) or FoundationOne in the Clinical Laboratory Improvement Amendments-certified laboratory in the USA. Response evaluations were performed according to RECIST v1.1. Four specimens did not pass the DNA quality test and 32 specimens were successfully sequenced with CCP (n = 31) and FoundationOne (n = 1). Of the 32 sequenced patients, 10 (31.3%) were ≤40 years. Twelve patients (37.5%) had received ≥3 types of prior systemic therapies. Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease). Nineteen of 24 patients with actionable mutations could not undergo targeted therapy based on genomic testing because of declining performance status (10/24, 41.7%), stable disease with previous treatment (5/24, 20.8%), and lack of access to targeted medication (4/24, 16.7%). NGS-based targeted therapy may be a good option in selected patients with refractory solid tumors. To pursue this strategy in Korea, lack of access to clinical-grade NGS assays and a limited number of genotype-matched targeted medications needs to be addressed and resolved.