Evaluation of Omics-Based Strategies for the Management of Advanced Lung Cancer

Abstract

<jats:sec><jats:title>PURPOSE:</jats:title><jats:p> Omic-informed therapy is being used more frequently for patients with non–small-cell lung cancer (NSCLC) being treated on the basis of evidence-based decision-making. However, there is a lack of a standardized framework to evaluate those decisions and understand the association between omics-based management strategies and survival among patients. Therefore, we compared outcomes between patients with lung adenocarcinoma who received omics-driven targeted therapy versus patients who received standard therapeutic options. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS:</jats:title><jats:p> This was a retrospective study of patients with advanced NSCLC adenocarcinoma (N = 798) at City of Hope who received genomic sequencing at the behest of their treating oncologists. A thoracic oncology registry was used as a clinicogenomic database to track patient outcomes. </jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p> Of 798 individuals with advanced NSCLC (median age, 65 years [range, 22-99 years]; 60% white; 50% with a history of smoking), 662 patients (83%) had molecular testing and 439 (55%) received targeted therapy on the basis of the omic-data. A fast-and-frugal decision tree (FFT) model was developed to evaluate the impact of omics-based strategy on decision-making, progression-free survival (PFS), and overall survival (OS). We calculated that the overall positive predictive value of the entire FFT strategy for predicting decisions regarding the use of tyrosine kinase inhibitor–based targeted therapy was 88% and the negative predictive value was 96%. In an adjusted Cox regression analysis, there was a significant correlation with survival benefit with the FFT omics-driven therapeutic strategy for both PFS (hazard ratio [HR], 0.56; 95% CI, 0.42 to 0.74; P &lt; .001) and OS (HR, 0.51; 95% CI, 0.36 to 0.71; P &lt; .001) as compared with standard therapeutic options. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION:</jats:title><jats:p> Among patients with advanced NSCLC who received care in the academic oncology setting, omics-driven therapy decisions directly informed treatment in patients and was correlated with better OS and PFS. </jats:p></jats:sec>

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

“…As expected, this was significantly worse than those who received any TKI during the therapy course (median: not reached, p < 0.001). This is consistent with almost every similar study denoting the importance of offering mutation-guided therapy as early as possible during the disease course [17][18][19]. Subsequently, the lack of molecular testing in stage IV nonsquamous NSCLC may be associated with a shorter OS.…”

Assessing Oncologists’ Attitudes Concerning Comprehensive Genomic Profiling in Stage IV Lung Adenocarcinoma in Brazil

“…Most guidelines endorse somatic genomic testing in LUAD because of the potential to affect therapy: approximately 60% of patients have genomic driver alterations, and several studies reveal that using genomic testing to implement guideline-concordant targeted treatment improves long-term outcomes in patients with oncologic malignancies. 18 , 19 Nevertheless, extensive literature suggests that genomic test use is still far from ideal. As few as 15% of patients with LUAD treated in the community setting in the United States undergo CGP, with greater than 30 genes tested.…”

Precision Oncology Beyond Genomics: The Future Is Here—It Is Just Not Evenly Distributed

“…Beyond the generation of data and the potential use of sophisticated in vitro models, the even more challenging task is to identify and select the most meaningful omics data types to apply (limited primarily by time, cost and tissue availability) and in a second step to establish best-practice approaches to integrate the different datasets to obtain a comprehensive picture of the underlying biological processes (Figure 2). Very recent publications evaluating omics-based strategies for guiding the clinical management of difficult-to-treat tumors fuel hope to overcome the challenges of ITH [141]. In the long run, applying multiple omics-technologies may have the same significance for deciphering intra-tumor heterogeneity as the Rosetta stone had for learning how to read and interpret ancient hieroglyphs.…”