Clinical Utility of Genomic Profiling Tests in Patients with Advanced Gastrointestinal Cancers

• Published in: Targeted oncology Vol. 17; no. 2; pp. 177 - 185
• Main Authors: Takeda, Hiroyuki, Imoto, Kiyomi, Umemoto, Kumiko, Doi, Ayako, Arai, Hiroyuki, Horie, Yoshiki, Mizukami, Takuro, Oguri, Tomoyo, Ogura, Takashi, Izawa, Naoki, Yamamoto, Hiroyuki, Yamano, Yoshihisa, Sunakawa, Yu
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2022; Springer Nature B.V
• Subjects: Biomarkers, Tumor - genetics; Biomedicine; Brain cancer; Cancer therapies; Gastrointestinal cancer; Gastrointestinal Neoplasms - genetics; Genes; Humans; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Original Research Article; Patients; Proto-Oncogene Proteins B-raf - genetics; Retrospective Studies; Software
• DOI: 10.1007/s11523-022-00871-4
• ISSN: 1776-2596; 1776-260X

Background Comprehensive analyses of cancer-related genomic alterations are expected to lead to increased availability of targeted therapies. However, in patients with gastrointestinal (GI) cancers, the utility of genomic profiling is unclear because of common non-druggable alterations and rapid disease progression that prevent a sufficient time period to seek targets. Objective The aim of this study was to determine the utility of genomic profiling tests in patients with GI cancers. Methods The subjects of this retrospective study were patients with GI cancers and patients with non-GI cancers who underwent tissue-based genomic profiling at a single institution from April 2017 to October 2020. The profile of gene alterations, frequency of tumor mutational burden-high (≥ 10 Muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers. Results In all, 133 patients with GI cancers and 63 patients with non-GI cancers were included. The genomic profiles of GI cancers showed the highest frequencies of TP53 , KRAS , and APC mutations and a significantly lower frequency of PIK3CA mutations than those of non-GI cancers. Tumor mutational burden-high was significantly less prevalent in GI cancers (4% vs 20%, p = 0.008). Twenty-nine patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies based on the findings. Among them, seven patients each with GI cancers and non-GI cancers received the recommended therapy on their genomic findings, which showed similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%, p = 0.791). HER2-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers. Conclusions Although their genomic profiles revealed fewer druggable sites, patients with GI cancers accessed targeted therapies similarly to patients with non-GI cancers. The utility of genomic profile testing in patients with GI cancers was highlighted to determine if patients can receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.