Abstract 2552: Real-world analysis of biomarker testing and use of targeted therapies in metastatic non-small cell lung cancer (mNSCLC) in the United States (US)
Authors: Michael J. Dennis, Devin Abrahami, Maria Cecilia Vieira, Darrin Benjumea, Marley Boyd, Anran Shao, Kirsten Duncan, John Kelton, Sandip P. Patel
Journal: Cancer Research (2024)

Abstract Background: Between 1998 and 2022, over 40% of new oncology drugs approved by the US FDA were precision therapies. In nonsquamous mNSCLC, detecting biomarkers where targeted therapies exist (EGFR, ALK, ROS1, BRAF V600E variant, MET exon 14 skipping variant, RET and PD-L1) has become essential for adequate clinical care. This study investigated real-world use of these biomarker tests, their characteristics, and associated use of targeted therapies in mNSCLC patients in the US. Methods: Adults ≥18 years old with stage IV mNSCLC from the nationwide Flatiron Health electronic health record-derived de identified database (01/2011 - 04/2023). The proportion of patients receiving biomarker tests, timing, characteristics, test type (single, multiple or next-generation sequencing), and proportion of patients receiving guideline recommended associated targeted therapies (i.e. actionable treatment) was assessed. Actionable treatment was defined in study years where at least one actionable therapy was FDA approved (biomarker, therapy, date: ALK, crizotinib, Aug 2011; BRAF V600E, dabrafenib+trametinib, Jul 2015; EGFR, afatinib, Jul 2013; MET exon 14 skipping, capmatinib, May 2020; PD-L1, pembrolizumab, Oct 2015; RET, pralsetinib, Sep 2020; ROS-1, crizotinib, Mar 2016). Results: In 42,037 patients with mNSCLC, the proportion of patients receiving each test were: ALK: 71.6%, BRAF: 48.8%, EGFR: 74.9%, MET: 41.4%, PD-L1: 49.3%, RET: 42.3%, and ROS1: 54.2%. Median (Q1, Q3) time from mNSCLC diagnosis to first biomarker result was 21 (12, 37) days. Tissue was the most common sample type for biomarker testing, although sampling by blood has increased in recent years. Multiple testing methods were more common in ALK and PD-L1 (48.1% and 50.3%, respectively) and next generation sequencing was more common in the other biomarkers (BRAF: 77.7%, EGFR: 57.1%, MET: 74.1%, RET: 70.7%, ROS1: 54.0%). Testing rates increased from 2011 through 2023 for each biomarker, with the highest rates in 2023: ALK (87.7%), BRAF (85.2%), EGFR (88.7%), MET (85.7%), PDL1 (78.7%), RET (84.8%), and ROS1 (86.9%). Testing rates were similar when timing was restricted to a 1-year window from mNSCLC diagnosis. Receipt of actionable treatment varied by biomarker, in order of increasing frequency: RET+ (23.0%), MET+ (34.0%), BRAF+ (42.7%), PDL1+ (56.3%), ROS1+ (59.8%), EGFR+ (70.6%), and ALK+ (89.0%). Generally, across all biomarkers, receipt of actionable therapy increased in more recent years. Conclusion: Current real-world biomarker testing rates and use of actionable treatments may reflect increased adoption of clinical guideline recommendations. Despite increased testing, use of actionable therapy remains low for certain biomarkers. Further improvements in the implementation of robust biomarker testing to use appropriate therapies are needed, which can lead to better patient outcomes. Citation Format: Michael J. Dennis, Devin Abrahami, Maria Cecilia Vieira, Darrin Benjumea, Marley Boyd, Anran Shao, Kirsten Duncan, John Kelton, Sandip P. Patel. Real-world analysis of biomarker testing and use of targeted therapies in metastatic non-small cell lung cancer (mNSCLC) in the United States (US) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2552.