Abstract
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.
Highlights
In Korea, a total of around 200,000 new solid tumor cases and around 66,000 solid tumor deaths were reported in 2012 [1]
Everolimus is approved for the treatment of renal cell carcinoma by Korea Food and Drug Administration; in this study, everolimus was used in parotid carcinosarcoma and tracheal squamous cell carcinoma with PIK3CA mutation
Eleven non-small cell lung cancer (NSCLC) (34.4%) patients (10 adenocarcinomas and one neuroendocrine carcinoma) and four (12.4%) esophageal cancer patients were enrolled, and patients with various tumor types were enrolled in small numbers
Summary
In Korea, a total of around 200,000 new solid tumor cases and around 66,000 solid tumor deaths were reported in 2012 [1]. Systemic chemotherapy is the standard treatment for these advanced cancer patients. Many patients have treatment failure after standard therapy. These refractory solid tumor patients have few anti-cancer treatment options. Many of these patients pay high costs for unproven treatments, such as traditional medicines, but still do not have an improved survival in advanced solid tumors [2]. In Korea, the cost of alternative medicine in cancer patients increased from 621 to 1,388 (million US$, per year) during 2000–2010 [3]. Development of effective therapeutic strategies for refractory solid tumors is a huge unmet medical need
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