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Original Investigation
August 7, 2018

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

Author Affiliations
  • 1The Ohio State University, Medical Oncology, Columbus
  • 2Yale School of Public Health, New Haven, Connecticut
  • 3Yale School of Medicine, New Haven, Connecticut
  • 4Flatiron Health, New York, New York
  • 5New York University School of Medicine, New York
  • 6Stanford University School of Medicine, Stanford, California
JAMA. 2018;320(5):469-477. doi:10.1001/jama.2018.9824
Key Points

Question  Is there an association between broad-based genomic sequencing and better survival compared with routine genomic testing (EGFR/ALK alterations only) among patients with advanced non–small cell lung cancer treated in the community oncology setting?

Findings  In this retrospective cohort study that included 191 community oncology practices and 5688 patients, there was no significant association between broad-based genomic sequencing and routine genomic testing on 12-month mortality using instrumental variable analysis (difference, −3.6%) or overall survival using a propensity score–matched analysis (hazard ratio, 0.92).

Meaning  Use of broad-based genomic sequencing in the community setting for advanced non–small cell lung cancer may not currently offer a survival advantage.


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 unmatched cohort (hazard ratio, 0.69 [95% CI, 0.62 to 0.77]; log-rank P < .001).

Conclusions and Relevance  Among patients with advanced non–small cell lung cancer receiving care in the community oncology setting, broad-based genomic sequencing directly informed treatment in a minority of patients and was not independently associated with better survival.