Half of oncologists fail to use ordered NGS results to guide their first-line treatment decision in advanced NSCLC: A retrospective study in a community-based integrated healthcare system

Abstract

Purpose: Next generation sequencing (NGS) testing is used to identify driver mutation(s) in non-small cell lung cancer (NSCLC) that are amenable to targeted therapy, resulting in superior outcomes and improved tolerability. We characterized how clinicians in a large integrated healthcare system utilized NGS testing to inform first line treatment decisions in patients with stage IV NSCLC shortly after diagnosis. Methods: We conducted a cross-sectional study of 964 patients within an integrated healthcare system, Kaiser Permanente Southern California (KPSC), who were diagnosed with stage IV NSCLC and completed NGS testing (Strata Oncology) between May 2019 to June 2021. Treatment start dates were used to divide patients into those who started treatment before or after NGS results, or those who did not receive treatment after NGS results. Patients harboring alterations in seven genes (EGFR, ALK, ROS-1, BRAF, KRAS, RET, and MET) were considered candidates for targeted first line therapy. Results: First line treatment was initiated in half (52 %; n = 284) of all treated patients prior to NGS results. Just under half (48 %; n = 137) of these patients were found to have a targetable mutation by NGS, of whom 59 % received first line chemotherapy and/or immunotherapy, rather than targeted therapy. Nearly 27 % of the sample never received treatment, of which 31 % had a targetable mutation, and may have been candidates for targeted therapy. Not undergoing first line treatment was correlated with older age, higher comorbidity index, smoking history, and the lack of an identifiable driver mutation. Conclusion: NGS tests results were not exclusively used to inform first line treatment decisions in most patients with stage IV NSCLC, and most patients with a targetable mutation were not treated with targeted therapy. Possible explanations include lengthy turnaround times for NGS testing and the availability of timelier but less accurate single gene testing.