Impact of reflexive next-generation sequencing on treatment initiation in non–small cell lung cancer.

e20096 Background: Timely identification of actionable mutations is critical for guiding targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). In previous work, our group has shown that reflexive next generation sequencing (NGS), where molecular testing is initiated by pathology at the time of diagnosis, resulted in a 40.6% reduction in NGS reporting time. In this retrospective study, we investigated whether these improvements were associated with improvements in diagnostic to treatment timelines and downstream clinical care metrics among patients with NSCLC. Methods: We conducted a retrospective cohort study of patients diagnosed with NSCLC who underwent NGS testing during their diagnostic evaluation (N = 49). Time zero was defined as the specimen collection date from biopsy/surgical resection to initiation of treatment. We used Foundation One Companion Diagnostic (CDx) to identify tumor mutation profiles to detect biomarkers with FDA-approved targeted therapies. Patients who did not undergo oncology evaluation or who had insufficient clinical data due to early death were excluded. Key intervals consisted of biopsy to finalized NGS report and biopsy to treatment initiation. Continuous variables were summarized using medians and interquartile ranges (IQRs) and compared using Mann-Whitney U tests. Categorical variables were compared using Fisher’s exact test. Results: A total of 42 patients with NSCLC were included in the analysis, including 22 patients in the non-reflexive NGS cohort and 20 patients in the reflexive NGS cohort. The median age at diagnosis was 69.5 years range 32-85. Most patients presented with advanced-stage disease, with stage IV disease in 27 patients (64.2%), stage III in 9 patients (21.4%), and early-stage disease (stage I-II) in 6 patients (14.2%). Among patients with systemic therapy treatments, reflexive testing was associated with a shorter time from biopsy to treatment initiation (median 34.0 days IQR 31.0-36.5 vs 51.5 days IQR 38.5-63.5, p = 0.009). Molecular profiling results were available prior to initiation of first-line therapy in 100% of patients in the reflexive group compared with 83.3% in the non-reflexive group. Acute care visits and hospitalizations did not differ significantly between reflexive and non-reflexive cohorts, although a nonsignificant trend toward fewer acute care visits was observed in the reflexive group. Conclusions: Reflexive NGS implementation was associated with a significantly shorter diagnosis to treatment timeline and implement in molecular readiness at the time of treatment initiation. These improvements showed a significant reduction in time to initiation of appropriate and specific systemic therapy. These findings support reflexive molecular testing as a pragmatic, system level intervention to improve quality care by accelerating appropriate treatment decisions and care delivery in NSCLC.