Evaluation of Guideline-Recommended Care in First-Line Treatment for Advanced/Metastatic Non-Small Cell Lung Cancer Patients who underwent Next-Generation Sequencing Testing: Results from a Real-World Study

• Roughly 30% of patients with biomarker-positive disease did not receive the indicated 1L guideline-recommended targeted therapy despite availability of NGS test results prior to 1L initiation • Patients treated with 1L targeted therapy had the longest median overall survival • EHR-based alerts could help increase the uptake of biomarker-driven treatment • There is an unmet need for 1L treatment in a/mNSCLC, particularly for KRAS G12C & HER2 This study examined treatment patterns among patients with available next generation sequencing (NGS) results before starting first-line (1L) treatment, using either tissue-based (T-NGS) or blood-based (B-NGS) NGS testing in patients with advanced/metastatic non-small cell lung cancer (a/mNSCLC). This retrospective study included US patients aged ≥18 years with a/mNSCLC who received a T-NGS or B-NGS test and had results available prior to 1L. Most frequent (n≥40) treatment patterns were reported as sequence of treatments received in 1L through (→) second line (2L). Overall survival (OS) was measured from the date of NGS test result. Descriptive analyses were conducted separately in T-NGS and B-NGS, stratified by biomarker status. A total of 2980 (T-NGS, 1632; B-NGS, 1348) patients were eligible. The median age was 71 years, 52% female, 62% White, and 83% smokers. Approximately 32% (T-NGS, 35%; B-NGS, 32%) of patients were positive for biomarkers and receipt of targeted therapy (TT) in 1L was ≤68% (T-NGS, 67%; B-NGS, 70%). Median OS was longest for ‘TT → none’ in the biomarker-positive subgroups of both cohorts. Approximately 30% of patients with biomarker-positive disease did not receive the indicated 1L guideline-recommended TT despite availability of NGS test results prior to 1L initiation. These findings highlight variability in 1L treatment selection for patients with biomarker-positive a/mNSCLC and underscore the need for further research to understand barriers to TT use. Health systems should consider proactive, scalable solutions (e.g., EHR-based alerts) to ensure that biomarker-driven treatment is not just possible but reliably delivered.