Real-World Association Between Up-Front Next-Generation Sequencing and Overall Survival in Advanced Non–Small Cell Lung Cancer in the United States

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Abstract
Purpose: Clinical guidelines recommend next-generation sequencing (NGS) before initiation of first-line (1L) therapy as the standard of care for patients with advanced non–small cell lung cancer (aNSCLC). This study examined the impact of timing of molecular testing in relation to treatment initiation on overall survival (OS) to help inform clinical decision making for aNSCLC treatment. Methods: This retrospective cohort study analyzed the Flatiron Health aNSCLC deidentified database from 2019 to 2021. Patients with aNSCLC and 1L systemic therapy were grouped into three cohorts based on timing of testing: (1) up-front NGS; (2) up-front non-NGS genomic testing; and (3) NGS after 1L therapy initiation. Kaplan-Meier analysis and Cox Proportional Hazards models were used to compare OS from the date of aNSCLC diagnosis between cohorts. Results: Overall, 13,139 patients with aNSCLC treated with systemic therapy were identified, including 6,210 patients with up-front tumor NGS, 2,697 patients with up-front non-NGS testing, and 2,824 patients with NGS after 1L initiation. A higher proportion of patients with up-front NGS received targeted therapy compared with patients with NGS after 1L initiation (22.6% v 14.8%, P < .0001). Median OS was significantly longer (20.9 months) with up-front NGS compared with up-front non-NGS (17.5 months) and NGS testing after 1L (18.2 months, P < .005). Multivariable analyses suggest that OS benefits associated with up-front NGS were primarily attributable to treatment. Conclusion: NGS testing before 1L therapy was observed to be associated with earlier use of targeted therapy and longer survival when compared with other testing strategies. Future studies are warranted given the rapidly evolving treatment landscape in aNSCLC.

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