Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials

Abstract

Background. The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. Methods. CGP was performed to a mean coverage depth of 5763 on 6,832 consecutive cases of NSCLC (2012)(2013)(2014)(2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. Results. The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients

Molecular Epidemiology of <b><i>ALK</i></b> Rearrangements in Advanced Lung Adenocarcinoma in Latin America

“…Current guidelines recommend assessment of abnormalities involving several genes: EGFR and ALK remain the cornerstone, while others have been added including ROS-1 and BRAF v600 [29, 30]. In Latin America, as in many other resource-limited parts of the world, it has become increasingly difficult to define which biomarkers should be routinely tested in order to adequately select patients for targeted therapy and make the choice for the highest cost-effectiveness [31].…”

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications

“…A total of 65% patients in our study harbor mutations with available matched targeted therapeutic options, including 26% of patients with actionable mutations in genes recommended for cancer genetic testing by the NCCN guideline. In comparison to a previously published study [19], we not only focused on the clinical application of cancer genetic testing, but also utilized the accumulated data in a large cohort to identify novel oncogenic mutations in NSCLCs. Moreover, we integrated publicly available cancer genetic, genomic, and pharmacogenomic data sources to explore the clinical implication of novel mutations.…”

“…While the germline mutations are often overlooked by previously published clinical sequencing studies [19], we analyzed our cohort for germline mutations with potential clinical implications. For example, KIT p.M541L mutation detected in 146 (16%, 146/932) tumors and KDR p.Q472H mutation in 5 (0.5%, 5/932) tumors are associated with resistance to EGFR inhibitors in NSCLCs [37].…”

“…Emerging evidence has also demonstrated clinical benefit to therapies against BRAF [8][9][10][11], MET [12][13][14], RET [15,16], or HER2 [17,18] in patients harboring activating mutations in the corresponding targets. The clinical utility of cancer genomic profiling in NSCLCs has been demonstrated by a recent report of 6800 cases utilizing the FoundationOne® panel (http://foundationone.com/) to facilitate implementation of the NCCN guidelines for lung cancer biomarker testing [19]. The study identified 39% of the tested patients harbor mutations in at least one of the seven genes shown in NCCN guideline [19].…”

“…The clinical utility of cancer genomic profiling in NSCLCs has been demonstrated by a recent report of 6800 cases utilizing the FoundationOne® panel (http://foundationone.com/) to facilitate implementation of the NCCN guidelines for lung cancer biomarker testing [19]. The study identified 39% of the tested patients harbor mutations in at least one of the seven genes shown in NCCN guideline [19].…”