Abstract: Despite clear clinical benefit and guideline recommendations for predictive biomarker testing and subsequent first-line targeted therapy treatment in patients with non–small cell lung cancer (NSCLC), there is evidence that testing has not been widely embraced in the clinical setting. This study uses clinical pathways to understand biomarker testing patterns and ensuing first-line treatment decisions. Data of patients with metastatic NSCLC were analyzed for testing rates and treatment selection at 7 cancer programs using data input by providers into the pathways software. Findings were analyzed by type of provider (community or academic). Among providers using clinical pathways, biomarker testing rates were high and appropriate selection of targeted therapy was observed. Clinical pathways can act as a tool to assist oncology practices to promote testing of key biomarkers and subsequent selection of appropriate therapy.
In 2017, lung and bronchus cancer was the second-most common cancer type in the United States, representing 13% of all new cancer cases.1 Of the estimated 222,550 lung and bronchus cancer cases diagnosed in 2017, approximately 80% to 85% were non–small cell lung cancer (NSCLC).1,2 The vast majority of patients with NSCLC are diagnosed in the metastatic stage.1 While advancements in chemotherapy regimens have improved the overall survival rate in the past 3 decades, the 5-year, overall survival rate remains low (~17%).1,3 Advancements in diagnosis and treatment of NSCLC are critical to improving survival.
The recent identification of some of the driver mutations for NSCLC has allowed for more individualized targeted treatment options as compared with traditional cytotoxic chemotherapies. As a result, it is now a standard recommendation that patients with advanced NSCLC undergo routine molecular testing for identification of certain known genomic abnormalities, most notably, rearrangements of anaplastic lymphoma kinase (ALK) and mutations of epidermal growth factor receptor (EGFR).4,5 Tyrosine kinase inhibitors (TKIs) that target these abnormalities have provided greater clinical benefit with improved survival compared with cytotoxic treatments in patients with NSCLC. For instance, patients with NSCLC with somatic mutations in EGFR are demonstrated to have improved progression-free survival when treated with EGFR-targeted therapies compared with platinum-based chemotherapy.6-9 Similar results have been noted with treatments that target ALK and/or c-ros oncogene 1 (ROS1) rearrangements in patients with NSCLC bearing these molecular abnormalities.8,10-12 More recently, patients with NSCLC and bearing the BRAF V600 mutation have demonstrated clinical response to BRAF/MEK inhibitor therapy.13
In patients lacking these specific genomic abnormalities or in those who have progression after treatment with targeted therapy, expression of programmed death ligand 1 (PD-L1) may provide guidance regarding the use of immune checkpoint inhibitors that have provided major treatment responses across numerous cancer types, including NSCLC.14-16 PD-L1 expression does not have a universal standard, making it a less-than-ideal biomarker, but it is currently the best available method with which to assess a patient with NSCLC’s candidacy for treatment with pembrolizumab. Use of single-agent pembrolizumab in the first-line, NSCLC metastatic setting requires PD-L1 expression levels of 50% or more.14
The availability of treatments that specifically target genetic alterations leading to superior outcomes has led to the issuance of guidelines by the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology recommending testing for EGFR and ALK mutations and/or translocations at diagnosis of advanced stage NSCLC. Furthermore, the guidelines state that testing for alterations in EGFR and ALK should be prioritized over other molecular predictive tests.4 Additionally, the National Comprehensive Cancer Network® (NCCN) strongly recommends that patients with metastatic NSCLC undergo molecular testing for EGFR or ALK alterations and, if positive, receive targeted therapy in the first-line setting. The NCCN also recommends testing for ROS1 and BRAF as part of broad molecular profiling, in addition to PD-L1 expression levels, to guide first-line treatment decisions.17
A recent international survey of oncologists assessed the degree to which a patient with NSCLC’s genetic makeup impacted first-line treatment decisions by providers. The majority (60%) of oncologists in North America did not base their treatment decision on a patient’s genetic mutation subtype. Despite ordering mutation tests, 21% of North American-based oncologists determined the treatment regimen for their patients before the mutation test results were available. Overall, 23% of respondents did not consider EGFR mutation subtypes in making treatment decisions.18 An analysis of real-world patterns of EGFR testing and treatment based on a random sample of patients with NSCLC in the Surveillance Epidemiology and End Results database found that less than a quarter of the stage IV, adenocarcinoma patients received EGFR testing, and less than half with stage IV, EGFR-positive disease received targeted therapy.19 A separate study examining PD-L1 testing patterns and nivolumab and pembrolizumab use for all lines of metastatic NSCLC treatment found that, prior to receiving either nivolumab or pembrolizumab, 11.3% of patients were tested for PD-L1 expression.20 Despite clear evidence of the clinical benefits associated with molecular testing and the universal recommendations calling for molecular testing to guide treatment decisions, it is apparent that resources and processes are urgently needed to ensure appropriate implementation of molecular testing in the NSCLC-treatment setting.
One strategy to promote testing of actionable biomarkers and appropriate use of targeted agents is through the use of clinical pathways. Clinical pathways have been adopted in various fields of medicine, including congestive heart failure, pneumonia, chronic obstructive pulmonary disease, stroke, asthma, and deep vein thrombosis.21-26 A recent study in breast cancer demonstrated that clinical pathways have the ability to standardize clinical practice patterns and rapidly promote change consistent with current evidence-based guidelines.27 Another breast cancer study demonstrated that clinical pathways can be used to measure adoption of diagnostic testing and the use of appropriate therapy based on the results of diagnostic testing.28
In order to explore the ability of clinical pathways to promote testing of key biomarkers and subsequent appropriate use of targeted agents as treatment in patients with metastatic NSCLC, authors performed a retrospective data analysis to compare biomarker testing rates with treatment decisions at academic and community cancer programs utilizing the Via Oncology clinical pathways software program, the Via Portal.