Real-world concordance of clinical practice with ASCO and NCCN guidelines for EGFR/ALK testing in aNSCLC.

Abstract

212 Background: Timely and appropriate biomarker testing guides evidence-based treatment decision-making in advanced non-small cell lung cancer (aNSCLC). American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines recommend that all treatment-eligible patients with non-squamous, or squamous histology in non-smokers undergo EGFR and ALK biomarker testing prior to initiating first line therapy. Genentech’s Learning and Clinical Integration team and Flatiron Health explored the frequency of EGFR/ALK testing and overall time between advanced disease diagnosis, results receipt and treatment initiation in clinical oncology practices. Methods: Structured and unstructured data were obtained from Flatiron’s electronic health record database. 6,991 patients from 166 clinics diagnosed after 1/1/14 with at least 2 visits before 8/31/15 were randomly selected from the Flatiron aNSCLC national cohort of > 25,000 patients. Dates of specimen collection, results receipt and treatment start were collected. Results: EGFR/ALK testing was conducted in 75% of non-squamous patients with wide variation across practices (< 20% to 100%). For squamous patients, 15% were tested overall, but with dramatic variation across practices (0% to 100%). For patients with a positive test result available prior to initiation of first line treatment, 79% of EGFR+ and 94% of ALK+ patients received the appropriate targeted therapy. However, for those patients tested after initiation of first line therapy, only 41% of EGFR+ and 65% of ALK+ patients received appropriate targeted first line therapy. EGFR/ALK tests results were received > 4 weeks from aNSCLC diagnosis in 32% and 34% of patients, respectively. Validation testing indicated that delays were attributed to non-lab factors, as test results were returned in < 2 weeks in 95% of cases. Conclusions: Wide variation in real-world practice illustrates the need to improve adherence to ASCO and NCCN biomarker testing guidelines. Educational intervention to improve quality of care in aNSCLC should focus on ensuring testing of almost all non-squamous patients, limiting testing to the non-smoking squamous cell population, and ensuring timely ordering of testing by clinicians.

Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer

“…In a study of patients with newly diagnosed mNSCLC recruited from 15 community clinics, only 8% of 814 patients had complete tissue genotyping for all guideline-recommended biomarkers, with almost onethird not tested for EGFR mutations or ALK fusions, 75% untested for ROS1 fusions, and more than 80% untested for the BRAF V600E mutation, MET amplifications or exon 14 skipping alterations, RET fusions, or ERBB2 mutations (8). In a larger study conducted in 166 clinics, 25% of the almost 7,000 patients were not tested for EGFR mutations or ALK fusions (9). In this study, which represents an enriched Figure 2.…”

“…The increasing number of therapeutic biomarkers to be assessed in patients with newly diagnosed mNSCLC adds time to the clinical evaluation and places strain on tumor tissue availability, especially when biomarkers are assessed in a sequential manner adding additional expense (7). Real-world studies of clinical practice have demonstrated that significant numbers of patients with mNSCLC are not tested for the four guideline-recommended biomarkers with FDA-approved targeted therapies, EGFR exon 19 deletions and L858R mutation, BRAF V600E mutation, ALK fusions, and ROS1 fusions, and the majority are not tested for all eight guideline-recommended biomarkers (8,9). Utilizing comprehensive tissue next-generation sequencing (NGS) has shown promise in the ability to fully assess patients for the recommended biomarkers but remains challenged by tissue availability and the time required for guideline-complete testing.…”

Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey

“…Notably, median overall survival was lower for patients treated with chemotherapy, including those not tested for EGFRm and ALK, compared with patients treated with targeted therapy: 12.7 vs. 31.8 months, respectively (7). In a real-world analysis of 166 US community oncology practices from January 2014 to August 2015, only 41% and 65% of patients with EGFRm and ALK+ advanced NSCLC, respectively, were treated with targeted therapy when tested after initiation of first-line therapy, compared with 79% and 94% of patients, respectively, treated with targeted therapy when tested before initiation of first-line therapy (54).…”

Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

“…The implementation of molecular testing at the time of diagnosis in patients with advanced stage and the administration of molecular targeted agents nearly doubles the median of overall survival (OS) of patients with oncogenic-driven NSCLC. Moreover, it prevents the use of ineffective immunotherapies in this subgroup of patients [56]. However, an exhaustive molecular portrait by using a gene sequencing panel or by searching only specific molecular alterations of interest for the…”