Next-Generation Sequencing-Based Testing Among Patients With Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer in the United States: Predictive Modeling Using Machine Learning Methods

Background: Next-generation sequencing (NGS) has become a cornerstone of treatment for lung cancer and is recommended in current treatment guidelines for patients with advanced or metastatic disease. Objective: This study was designed to use machine learning methods to determine demographic and clinical characteristics of patients with advanced or metastatic non-small cell lung cancer (NSCLC) that may predict likelihood of receiving NGS-based testing (ever vs never NGS-tested) as well as likelihood of timing of testing (early vs late NGS-tested). Methods: Deidentified patient-level data were analyzed in this study from a real-world cohort of patients with advanced or metastatic NSCLC in the United States. Patients with nonsquamous disease, who received systemic therapy for NSCLC, and had at least 3 months of follow-up data for analysis were included in this study. Three strategies, logistic regression models, penalized logistic regression using least absolute shrinkage and selection operator penalty, and extreme gradient boosting with classification trees as base learners, were used to identify predictors of ever versus never and early versus late NGS testing. Data were split into D1(training+validation; 80%) and D2 (testing; 20%) sets; the 3 strategies were evaluated by comparing their performance on multiple m=1000 splits in the training (70%) and validation data (30%) within the D1 set. The final model was selected by evaluating performance using the area under the receiver operating curve while taking into account considerations of simplicity and clinical interpretability. Performance was re-estimated using the test data D2. Results: A total of 13,425 met the criteria for the ever NGS-tested, and 17,982 were included in the never NGS-tested group. Performance metrics showed the area under the receiver operating curve evaluated from validation data was similar across all models (77%-84%). Among those in the ever NGS-tested group, 84.08% (n=11,289) were early NGS-tested, and 15.91% (n=2136) late NGS-tested. Factors associated with both ever having NGS testing as well as early NGS testing included later year of NSCLC diagnosis, no smoking history, and evidence of programmed death ligand 1 testing (all P<.05). Factors associated with a greater chance of never receiving NGS testing included older age, lower performance status, Black race, higher number of single-gene tests, public insurance, and treatment in a geography with Molecular Diagnostics Services Program adoption (all P<.05). Conclusions:Predictors of ever versus never as well as early versus late NGS testing in the setting of advanced or metastatic NSCLC were consistent across machine learning methods in this study, demonstrating the ability of these models to identify factors that may predict NGS-based testing. There is a need to ensure that patients regardless of age, race, insurance status, and geography (factors associated with lower odds of receiving NGS testing in this study) are provided with equitable access to NGS-based testing.