Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting

• Published in: JAMA : the journal of the American Medical Association 2018-08, Vol.320 (5), p.469-477
• Main Authors: Presley, Carolyn J, Tang, Daiwei, Soulos, Pamela R, Chiang, Anne C, Longtine, Janina A, Adelson, Kerin B, Herbst, Roy S, Zhu, Weiwei, Nussbaum, Nathan C, Sorg, Rachael A, Agarwala, Vineeta, Abernethy, Amy P, Gross, Cary P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - therapy; Clinical outcomes; Cohort analysis; Communities; DNA, Neoplasm - analysis; Female; Gene sequencing; Genes, erbB-1; Genomics; Genotype; Humans; Immunotherapy; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Male; Medical screening; Middle Aged; Mortality; Mutation; Neoplasm Staging; Non-small cell lung carcinoma; Oncology; Original Investigation; Receptor Protein-Tyrosine Kinases - genetics; Retrospective Studies; Sequence Analysis, DNA; Survival; Survival Analysis
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2018.9824

IMPORTANCE: Broad-based genomic sequencing is being used more frequently for patients with advanced non–small cell lung cancer (NSCLC). However, little is known about the association between broad-based genomic sequencing and treatment selection or survival among patients with advanced NSCLC in a community oncology setting. OBJECTIVE: To compare clinical outcomes between patients with advanced NSCLC who received broad-based genomic sequencing vs a control group of patients who received routine testing for EGFR mutations and/or ALK rearrangements alone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of patients with chart-confirmed advanced NSCLC between January 1, 2011, and July 31, 2016, and who received care at 1 of 191 oncology practices across the United States using the Flatiron Health Database. Patients were diagnosed with stage IIIB/IV or unresectable nonsquamous NSCLC who received at least 1 line of antineoplastic treatment. EXPOSURES: Receipt of either broad-based genomic sequencing or routine testing (EGFR and/or ALK only). Broad-based genomic sequencing included any multigene panel sequencing assay examining more than 30 genes prior to third-line treatment. MAIN OUTCOMES AND MEASURES: Primary outcomes were 12-month mortality and overall survival from the start of first-line treatment. Secondary outcomes included frequency of genetic alterations and treatments received. RESULTS: Among 5688 individuals with advanced NSCLC (median age, 67 years [interquartile range, 41-85], 63.6% white, 80% with a history of smoking); 875 (15.4%) received broad-based genomic sequencing and 4813 (84.6%) received routine testing. Among patients who received broad-based genomic sequencing, 4.5% received targeted treatment based on testing results, 9.8% received routine EGFR/ALK targeted treatment, and 85.1% received no targeted treatment. Unadjusted mortality rates at 12 months were 49.2% for patients undergoing broad-based genomic sequencing and 35.9% for patients undergoing routine testing. Using an instrumental variable analysis, there was no significant association between broad-based genomic sequencing and 12-month mortality (predicted probability of death at 12 months, 41.1% for broad-based genomic sequencing vs 44.4% for routine testing; difference −3.6% [95% CI, −18.4% to 11.1%]; P = .63). The results were consistent in the propensity score–matched survival analysis (42.0% vs 45.1%; hazard ratio, 0.92 [95% CI, 0.73 to 1.11]; P = .40) vs unmatche