Impact of Molecular Biomarker Test Availability and Timing on Metastatic Non-Small-Cell Lung Cancer Treatment Selection and Clinical Outcomes in the U.S. Medicare Population

Abstract

Background: Advanced/metastatic non-small-cell lung cancer (mNSCLC) is associated with significant mortality. Molecular testing for selected oncogenes holds the promise of more effective targeted therapy versus systemic chemotherapies. This retrospective claims-based study examines timing of biopsy and molecular testing, treatment selection relative to biomarker status, and overall survival. Methods: Medicare data for patients with newly diagnosed mNSCLC were linked with molecular testing results from the Prognos NSCLC Explorer Dataset, including alterations implicated in NSCLC. Intervals between diagnosis, tissue acquisition, availability of test results, and initiation of treatment were calculated. Patients with actionable biomarker test results were compared with respect to treatment selection and overall survival. Cox proportional hazards regression was used to assess the likelihood of mortality between treatments. Results: A total of 11,407 patients qualified for analysis (Mean age±SD: 75.6±6.5 years; 50.7% female; 86.2% White). Biopsy was conducted between 2-12 days after clinical diagnosis, and biomarker results were typically available within three weeks. Initial treatment started soon after, and 63.4% of patients initiated first line of treatment (1LOT). Of 21.5% patients with actionable genomic testing results for ALK, BRAF, EGFR, KRAS, MET, NTRK, RET, or ROS1, use of targeted therapy (28%) was limited compared with immune checkpoint inhibitors (39%) and chemotherapies (33%). Of 78.5% without molecular alterations, lower use of both targeted therapy (24%) and immune checkpoint inhibitors (36%) and greater use of chemotherapy (40%) were observed. Patients with actionable mutations on targeted therapy were observed to have higher survival compared to other therapies. Hazard death ratios [Confidence Intervals] were significantly greater in patients receiving an immune checkpoint inhibitor (1.365[1.102-1.690]; p<0.05) and higher, although non-significantly, among chemotherapy (1.164[0.932-1.453]) recipients. Conclusions: Biomarker mutation status was available for many mNSCLC patients. Relatively short intervals between diagnosis of metastatic disease, biopsy, receipt of test results, and start of therapy were observed. Targeted therapy was associated with a higher overall survival when compared to both immune checkpoint inhibitors and chemotherapy. These findings support the expanded use of molecular biomarker testing in patients with newly diagnosed mNSCLC. The availability of actionable biomarkers appears to guide selection of 1LOT toward targeted therapy with improved survival.