Biomarker Testing Research Articles

HSR24-170: Utilization of Biomarker Testing and Biomarker-Driven Targeted Therapy Among Patients With Metastatic Non-Small Cell Lung Cancer.

HSR24-170: Utilization of Biomarker Testing and Biomarker-Driven Targeted Therapy Among Patients With Metastatic Non-Small Cell Lung Cancer.

Noninvasive and Multiplex Self-Test of Kidney Disease Biomarkers with Graphene-Based Lab-on-a-Chip (G-LOC): Toward Digital Diagnostics in the Hands of Patients.

Chronic kidney disease is one of the major health issues worldwide. However, diagnosis is now highly centralized in large laboratories, resulting in low access to patient monitoring and poor personalized treatments. This work reports the development of a graphene-based lab-on-a-chip (G-LOC) for the digital testing of renal function biomarkers in serum and saliva samples. G-LOC integrates multiple bioelectronic sensors with a microfluidic system that enables multiplex self-testing of urea, potassium, sodium, and chloride. The linearity, limit of detection (LOD), accuracy, and coefficient of variability (CV) were studied. Accuracy values higher than 95.5% and CV lower than 9% were obtained for all of the biomarkers. The analytical performance was compared against three reference lab benchtop analyzers by measuring healthy- and renal-failure-level samples of serum. From receiver operating characteristic (ROC) plots, sensitivities (%) of 99.7, 97.6, 99.1, and 89.0 were obtained for urea, potassium, sodium, and chloride, respectively. Then, the test was evaluated in noninvasive saliva samples and compared against reference methods. Correlation and Bland-Altman plots showed good correlation and agreement of the G-LOC with the reference methods. It is noteworthy that the precision of G-LOC was similar to better than benchtop lab analyzers, with the advantage of being highly portable. Finally, a user testing study was conducted. The analytical performance obtained with untrained volunteers was similar to that obtained with trained chemists. Additionally, based on a user experience survey, G-LOC was found to have very simple usability and would be suitable for at-home diagnostics.

Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort.

Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched for MET exon-14 skipping alterations and presented a lower prevalence of BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboring EGFR, KRAS, MET alterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients' selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.

Apolipoprotein E Genetic Testing in a New Age of Alzheimer Disease Clinical Practice.

The recent FDA approval of amyloid-lowering drugs is changing the landscape of Alzheimer disease (AD) clinical practice. Previously, apolipoprotein E (APOE) genetic testing was not recommended in the care of people with AD because of limited clinical utility. With the advent of amyloid-lowering drugs, APOE genotype will play an important role in guiding treatment recommendations. Recent clinical trials have reported strong associations between APOE genotype and the safety and possibly the efficacy of amyloid-lowering drugs. Therefore, a clinical workflow that includes biomarker and genetic testing should be implemented to provide patients with the opportunity to make informed decisions and instruct safety monitoring for clinicians. Pretest consent, education, and counseling will be an essential aspect of this process for patients and their family members to understand the implications of these tests and their results. Given that the approved amyloid-lowering drugs are indicated for patients with mild cognitive impairment or mild dementia with biomarker evidence of AD, biomarker testing should be performed before genetic testing and genetic testing should only be performed in patients interested in treatment with amyloid-lowering drugs. It is also important to consider other implications of genetic testing, including burden on and need for additional training for clinicians, the role of additional providers, and the potential challenges for patients and families.

Personal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective.

We described patients' and care partners' experiences with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing and result disclosure in routine care. IMPACT-AD BC is an observational study of clinic patients who underwent AD CSF biomarker testing as part of their routine medical care (n = 142). In the personal utility arm of the study, semi-structured phone interviews were conducted with a subset of patients (n = 34), and separately with their care partners (n = 31). Post-disclosure interviews were conducted ∼1 month and ∼6 months after biomarker result disclosure and investigated the patients' decision-making process around testing, impact of receiving results, wellness and lifestyle changes, and future planning. A majority of patients (90%) rated their decision to undergo testing as "easy." Post-disclosure, the majority (82%) reported overall positive feelings from having greater certainty and the ability to plan ahead, and results spurred them to adopt/continue healthy behaviors such as exercise (84%) and cognitive activities (54%). Care partners expressed relief from having more diagnostic certainty, increased appreciation of future caregiving responsibilities, and a desire to connect with support resources. Perspectives of persons with lived experience in dementia provide new insight into the value of biomarker testing and should be included as part of evidence-guided considerations for pre-test counseling and result disclosure. Moreover, study findings identify an interval when patients and care partners are highly receptive to positive lifestyle and medical interventions.

Clinical value of Alzheimer's disease biomarker testing.

In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Flexible electronic materials and devices toward portable immunoassays

AbstractBiomarker identification is a tried‐and‐true method that can provide precise biological information for disease diagnosis. Prompt diagnosis, disease progression monitoring, therapy efficacy evaluation, and prognosis assessment of cancers all benefit from sensitive, rapid, and precise measurement of significant biomarkers employing chemical and immunological approaches. The study of biomolecules and immunoassay evaluations can profit greatly from recent advancements in flexible electronic materials and technologies, which provide amazing flexibility, affordability, mobility, and integration. However, an overview of the implementation of portable immunoassays in conjunction with flexible electronic devices is rare to come by. This review focuses on recent breakthroughs in flexible electronic materials and devices for portable biomarker testing, which provides an extensive summary of flexible electrical components and sensing‐capable devices, emphasizing their adaptability in the construction of biosensing platforms. These platforms employ various signal transduction systems to record biological affinity recognition events, including pressure, temperature, electrical parameters, colorimetric signals, and other physical features. The challenges for portable, integrated, intelligent, and multifunctional immunoassays based on flexible sensing devices are also discussed. The portable immunoassays with flexible electronics would unlock the potential to transform clinical diagnostics into non‐clinical personalized treatments and achieve home‐based point‐of‐care testing for daily monitoring.

2 The role of cellular pathology departments in the improvement of turnaround times for lung adenocarcinoma biomarker testing

2 The role of cellular pathology departments in the improvement of turnaround times for lung adenocarcinoma biomarker testing

Molecular insights from comprehensive genomic profiling data in advanced metastatic colorectal cancer in South Asian population: A retrospective observational study

ABSTRACT Background: An increase in colorectal cancer incidence has been reported in India, often presenting in advanced stages and resulting in poor survival. However, the genomic and therapeutic landscape is not well understood. Objective: The primary objective of the study was to understand the mutational profile of metastatic colorectal cancer in the Southeast Asian cohort, and the secondary objective was to define the proportion of patients with therapeutically significant variants. Materials and Methods: This retrospective study was conducted between January 2021 and September 2023, at 4baseCare Onco Solutions Pvt. Ltd., Bengaluru, Karnataka, India. Comprehensive genomic profiling (CGP) and biomarker testing for MSI, TMB, and PD-L1 was carried out in 477 metastatic advanced (Stage III/IV) colorectal cancer patients, for the current retrospective-observational study. Results: With CGP, we identified drivers/clinically actionable variants in 78.6% of the cohort (375 patients). Although 30.8% of our cohort (147 patients) was eligible to available targeted therapy, 29.5% (141 patients) were found to harbor variants imparting therapeutic resistance. The combined mutation frequency of APC, TP53, and KRAS was >50%, while KRAS constituted >90% of all RAS mutations. The mismatch repair (MMR) genes including MLH1, MLH3, MSH3, and POLE were exclusively found in colon cancers. Genomic alterations in several genes of prognostic/therapeutic significance were seen (mutations in PIK3CA, SMAD4, BRAF, and amplifications in KRAS, EGFR, and ERBB2). Of those tested, 15.8% (41 patients) of the cohort had high tumor mutation burden (TMB-H), 14% had high microsatellite instability (MSI-H) (46 patients), and 26.8% were programmed death-ligand 1 (PD-L1) positive (30 patients). Conclusion: Our study shows that CGP is an advantageous option for identifying subsets of patients eligible for various targeted therapies, thus, improving patient outcomes.

Computational repurposing of oncology drugs through off-target drug binding interactions from pharmacological databases.

Systematic repurposing of approved medicines for another indication may accelerate drug development in oncology. We present a strategy combining biomarker testing with drug repurposing to identify new treatments for patients with advanced cancer. Tumours were sequenced with the Illumina TruSight Oncology 500 (TSO-500) platform or the FoundationOne CDx panel. Mutations were screened by two medical oncologists and pathogenic mutations were categorised referencing literature. Variants of unknown significance were classified as potentially pathogenic using plausible mechanisms and computational prediction of pathogenicity. Gain of function (GOF) mutations were evaluated through repurposing databases Probe Miner (PM), Broad Institute Drug Repurposing Hub (Broad Institute DRH) and TOPOGRAPH. GOF mutations were repurposing events if identified in PM, not indexed in TOPOGRAPH and excluding mutations with a known Food and Drug Administration (FDA)-approved biomarker. The computational repurposing approach was validated by evaluating its ability to identify FDA-approved biomarkers. The total repurposable genome was identified by evaluating all possible gene-FDA drug-approved combinations in the PM dataset. The computational repurposing approach was accurate at identifying FDA therapies with known biomarkers (94%). Using next-generation sequencing molecular reports (n=94), a meaningful percentage of patients (14%) could have an off-label therapeutic identified. The frequency of theoretical drug repurposing events in The Cancer Genome Atlas pan-cancer dataset was 73% of the samples in the cohort. A computational drug repurposing approach may assist in identifying novel repurposing events in cancer patients with no access to standard therapies. Further validation is needed to confirm a precision oncology approach using drug repurposing.

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

Advancing Precision-Targeted Treatment for Patients With Metastatic Non-Small Cell Lung Cancer.

At JADPRO Live 2023, presenters discussed the implications of biomarker testing, pivotal clinical trials leading to recent FDA approvals, and evidence-based best practices for monitoring and managing adverse events associated with molecular targeted and combination therapies for patients with metastatic non-small cell lung cancer.

Biomarkers for Early Prediction and Management of Preeclampsia: A Comprehensive Review.

Preeclampsia is a common complication of pregnancy. It is a multi-organ disorder that remains one of the main causes of maternal morbidity and mortality. Additionally, preeclampsia leads to many complications that can occur in the fetus or newborn. Preeclampsia occurs in about 1 in 20 pregnant women. This review focuses on the prediction of preeclampsia in women, using various biomarkers, in particular, a factor combining the use of soluble FMS-like tyrosinokinase-1 (sFlt-1) and placental growth factor (PlGF). A low value of the sFlt-1/PlGF ratio rules out the occurrence of preeclampsia within 4 weeks of the test result, and its high value predicts the occurrence of preeclampsia within even 1 week. The review also highlights other factors, such as pregnancy-associated plasma protein A, placental protein 13, disintegrin and metalloprotease 12, ß-human chorionic gonadotropin, inhibin-A, soluble endoglin, nitric oxide, and growth differentiation factor 15. Biomarker testing offers reliable and cost-effective screening methods for early detection, prognosis, and monitoring of preeclampsia. Early diagnosis in groups of women at high risk for preeclampsia allows for quick intervention, preventing the undesirable effects of preeclampsia. However, further research is needed to validate and optimize the use of biomarkers for more accurate prediction and diagnosis. This article aims to review the role of biomarkers, including the sFlt1/PlGF ratio, in the prognosis and management of preeclampsia.

Use of a Blood Biomarker Test Improves Economic Utility in the Evaluation of Older Patients Presenting with Cognitive Impairment.

More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer's disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD® blood test, a clinically validated BBM test for the evaluation of brain amyloid, a pathological hallmark of AD. The model compared 2 scenarios: (1) baseline testing involving usual care practice, and (2) early use of a BBM test before usual care CSF and PET biomarker use. At a modest 40% adoption rate, the BBM test scenario had comparable sensitivity and specificity to the usual care scenario and showed net savings in the diagnostic work-up of $3.57 million or $0.30 per member per month in a 1 million member population, translating to over $1B when extrapolated to the US population as a whole and representing a 11.4% cost reduction. Savings were driven by reductions in the frequency and need for CSF and PET testing. Additionally, BBM testing was associated with a cost savings of $643 per AD case identified. Use of the PrecivityAD blood test in the clinical care pathway may prevent unnecessary testing, provide cost savings, and reduce the burden on both patients and health plans.

The Importance of Biomarker Testing in the Treatment of Advanced Non-Small Cell Lung Cancer: A Podcast.

The identification of actionable biomarkers and development of targeted therapies have revolutionized the field of lung cancer treatment. In patients with advanced non-small cell lung cancer (NSCLC), biomarker testing can inform selection of effective targeted therapies as well as avoid therapies that are less likely to be effective in certain populations. A growing number of actionable targets, including those involving EGFR, ALK, ROS1, BRAF, MET, KRAS, NTRK, RET, HER2, and PD-L1, can be identified with biomarker testing. More than half of patients with advanced NSCLC have tumors that harbor genetic alterations that can be targeted. When these patients are treated with targeted therapy, survival and quality of life may be significantly improved. In addition, broad-based molecular testing may detect alterations identifying patients who are potentially eligible for current or future clinical trials. Comprehensive biomarker testing rates in communities are often low, and turnaround times for results can be unacceptably long. There is an unmet need for widespread, efficient, and routine testing of all biomarkers recommended by clinical guidelines. New testing techniques and technologies can make this an attainable goal. Panel-based sequencing platforms are becoming more accessible, and molecular biomarker analysis of circulating tumor DNA is becoming more common. In this podcast, we discuss the importance of biomarker testing in advanced NSCLC and explore topics such as testing methodologies, effect of biomarker testing on patient outcomes, emerging technologies, and strategies for improving testing rates in the United States. Supplementary file1 (MP4 121301 KB).

NIR-II fluorescence lateral flow immunosensor based on efficient energy transfer probe for point-of-care testing of tumor biomarkers

Fluorescence lateral flow immunoassay (LFA) has emerged as a powerful tool for rapid screening of various biomarkers owing to its simplicity, sensitivity and flexibility. It is noteworthy that fluorescent probe mainly determines the analytical performance of LFA. Due to the emission and excitation wavelengths are located in the visible region, most fluorophores are inevitably subject to light scattering and background autofluorescence. Herein, we reported a novel LFA sensor based on the second near-infrared (NIR-II) fluorescent probe with excellent anti-interference capability. The designed NIR-II probe was the Nd3+ and Yb3+ doped rare earth nanoparticles (RENPs) by employing Nd3+ as energy donor and Yb3+ as energy acceptor, which of the donor-acceptor energy transfer (ET) efficiency reached up to 80.7 %. Meanwhile, relying on the convenient and effective encapsulation strategy of poly(lactic-co-glycolic acid) (PLGA) microspheres to RENPs, the surface functionalized NIR-II probe (RE@PLGA) was obtained for subsequent bioconjugation. Benefiting from the optical advantages of NIR-II probe, this proposed NIR-II LFA displayed a good linear relationship ranging from 7 ng/mL to 200 ng/mL for the detection of α-fetoprotein (AFP), an important biomarker of hepatocellular carcinoma (HCC). The limit of detection (LOD) was determined as low as 3.0 ng/mL, which was of 8.3 times lower than clinical cutoff value. It is promising that LFA sensor based on this efficient RENPs probe provides new opportunities for high sensitive detection of various biomarkers in biological samples.

Evaluation of Fecal Inflammatory Biomarkers to Identify Bacterial Diarrhea Episodes: Systematic Review and Protocol for the Enterics for Global Health Shigella Surveillance Study.

The measurement of fecal inflammatory biomarkers among individuals presenting to care with diarrhea could improve the identification of bacterial diarrheal episodes that would benefit from antibiotic therapy. We reviewed prior literature in this area and describe our proposed methods to evaluate 4 biomarkers in the Enterics for Global Health (EFGH) Shigella surveillance study. We systematically reviewed studies since 1970 from PubMed and Embase that assessed the diagnostic characteristics of inflammatory biomarkers to identify bacterial diarrhea episodes. We extracted sensitivity and specificity and summarized the evidence by biomarker and diarrhea etiology. In EFGH, we propose using commercial enzyme-linked immunosorbent assays to test for myeloperoxidase, calprotectin, lipocalin-2, and hemoglobin in stored whole stool samples collected within 24 hours of enrollment from participants in the Bangladesh, Kenya, Malawi, Pakistan, Peru, and The Gambia sites. We will develop clinical prediction scores that incorporate the inflammatory biomarkers and evaluate their ability to identify Shigella and other bacterial etiologies of diarrhea as determined by quantitative polymerase chain reaction (qPCR). Forty-nine studies that assessed fecal leukocytes (n = 39), red blood cells (n = 26), lactoferrin (n = 13), calprotectin (n = 8), and myeloperoxidase (n = 1) were included in the systematic review. Sensitivities were high for identifying Shigella, moderate for identifying any bacteria, and comparable across biomarkers. Specificities varied depending on the outcomes assessed. Prior studies were generally small, identified red and white blood cells by microscopy, and used insensitive gold standard diagnostics, such as conventional bacteriological culture for pathogen detection. Our evaluation of inflammatory biomarkers to distinguish diarrhea etiologies as determined by qPCR will provide an important addition to the prior literature, which was likely biased by the limited sensitivity of the gold standard diagnostics used. We will determine whether point-of-care biomarker tests could be a viable strategy to inform treatment decision making and increase appropriate targeting of antibiotic treatment to bacterial diarrhea episodes.

Validity of galactin-3 in acromegaly: comparison with traditional markers.

Acromegaly occurs due to overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Galectin-3 (Gal-3) has recently emerged as a novel biomarker, related to IGF-1. This study aimed to assess Gal-3 in patients with acromegaly and compare its effectiveness with traditional biomarker tests. A randomized case control study conducted in a single center included 50 acromegaly patients and 40 apparently healthy subjects (HS) serve as control group matched both age and BMI. Laboratory test was measured by routine assay used in center. Gal-3, GH, and IGF-1 were measured by enzyme-linked immunosorbent assay (ELISA). There were 50 patients with an average age of 50.40 ± 12.229 (50% of males). Compared with HS, patients' serum GAL-3 levels have increased significantly. The serum GAL-3 exceeds 14.363 ng/ml, with a sensitivity of 100.0 and a specificity of 100.0. Furthermore, serum Gal-3 levels in combination with traditional tests (GH and IGF-1) by DeLoongs test had a significant difference in discriminating acromegaly more accurately than traditional tests. In a summary, this study recommended clinicians measure serum Gal-3 as biomarkers for patients with acromegaly. In addition, the result above shed light on role of Gal-3 on acromegaly pathogenesis and might provide a therapeutic target of acromegaly patients.

Abstract 3426: Real-world biomarker testing rates and trends among patients with advanced non-small cell lung cancer in the US

Abstract Background: Broad biomarker profiling before treatment initiation for non-small cell lung cancer (NSCLC) is recommended. Patients may not receive or receive inadequate biomarker testing before treatment initiation. This study assesses rates and trends of biomarker testing in community and academic oncology practices in the US. Methods: A descriptive cohort study was conducted using electronic health records from an NSCLC registry. Patients who initiated NSCLC treatment following diagnosis of advanced NSCLC (stage IIIB/IIIC/IV) from 01/01/2015-12/31/2021 were identified. Patient demographics (age, gender, race, region) along with histology type (squamous/non-squamous) and hospital type (academic/community) were included. The percentage of patients receiving tests for any of the nine biomarkers before and during therapy was calculated and compared. Results: 8,769 patients were identified with advanced NSCLC; 65.9% having non-squamous cell carcinoma; 22.4% having squamous cell carcinoma; 11.7% unknown. 13.4% of patients were from academic centers, 78.7% from community hospitals, 8.0% unknown. The majority (59%) were 65+ years; 47.3% were female. Overall, 83.2% had biomarker testing at some point in treatment; only 66.3% before treatment initiation. Over time, biomarker testing rates prior to treatment initiation increased (46.9% in 2015 to 73.8% in 2021). The use of biomarker testing in non-squamous cell carcinoma was greater than in squamous cell carcinoma. The most frequent biomarker testing before treatment initiation were PD-L1 (52.2%), EGFR (51.6%), and ALK (50.7%), followed by ROS1 (46.9%), BRAF (39.5%), and KRAS (34.1%). Testing rates for the newest biomarkers NTRK, MET, and RET were 20.4%, 28.4%, and 28.0%, respectively. Testing rates were similar between academic centers and community-based hospitals, except for the newest biomarkers, where use in academic settings was greater. Biomarker testing rates were higher among female patients (χ2 P-value<0.001); rates by race were similar (χ2 P-value=0.83). Conclusion: While the use of biomarker testing in advanced NSCLC is growing, 26% of patients remained untested before treatment initiation. Biomarker testing in non-squamous cell carcinoma is higher than in squamous cell carcinoma, in keeping with the guideline emphasis on biomarker testing for that histology type. Results suggest that further dissemination of guideline recommendations to obtain biomarker test results prior to treatment initiation is important to optimize treatment decisions in the NSCLC landscape. Citation Format: Yiyu Chen, Angeline Carlson. Real-world biomarker testing rates and trends among patients with advanced non-small cell lung cancer in the 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 3426.

Abstract 6122: Disparities in biomarker testing practices in patients with metastatic non-small cell lung cancer (NSCLC) in the United States (US)

Abstract Background: Molecular testing is recommended in National Comprehensive Cancer Network guidelines for nonsquamous mNSCLC patients. While testing rates have been increasing, data from other tumor types suggest possible disparities in access to and use of biomarker testing. This study investigated real-world biomarker testing characteristics stratified by demographics for the EGFR, ALK, ROS-1, BRAF, MET, RET, and PD-L1 biomarkers in US patients diagnosed with mNSCLC. Methods: This study of adults ≥18 years old with stage IV mNSCLC used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database (01/2011-04/2023). Biomarker testing rate (i.e., proportion of patients with mNSCLC with at least one biomarker test) was quantified. Unadjusted biomarker testing rates were assessed in groups of patients stratified by demographic and clinical characteristics, including age group, sex, race, insurance type, Eastern Cooperative Oncology Group (ECOG) performance status (PS), smoking status, histology, and US region. Results: In 42,037 patients with mNSCLC, 34,510 (82.1%) received at least one test. The rates for 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%. Yearly testing rates increased, with the most recent year suggesting that anywhere from 78.7% of patients to 88.7% of patients received a test for at least one biomarker, with PD-L1 and EGFR being the least and most frequently tested, respectively. Rates of testing varied by age group, with 87.2% of younger patients (ages 18 to <50) receiving a test compared to 80.8% of older patients (ages ≥80). Asian patients had the highest testing rate (91.5%) whereas Black and Hispanic/Latino patients had the lowest (80.8% and 80.6% respectively). 82.2% of White patients, the largest racial demographic in this dataset, received at least one test. Commercial health plans had a slightly higher testing rate compared to Medicare or Medicaid (87.1%, 81.6% and 81.2%, respectively). Rates decreased as ECOG PS increased; in patients with ECOG PS=0, 89.6% received a biomarker test, whereas in patients with ECOG PS=3 and ECOG PS=4, 81.1% and 76.3% received a test, respectively. Smoking status (current or former) was associated with less testing (80.7%) compared to patients with no history of smoking (91.1%), and patients with non-squamous histology were more frequently tested (88.0%) compared to squamous histology (61.2%). The differences by sex and region were marginal. Conclusion: This study provides contemporary data on real-world biomarker testing and disparities in mNSCLC in the US. Results suggest that more work can be done to evaluate and address disparity gaps in specific subsets, including Black and Hispanic patients and those with a current or former history of smoking. Citation Format: Michael J. Dennis, Devin Abrahami, Maria Cecilia Vieira, Darrin Benjumea, Marley Boyd, Anran Shao, Kirsten Duncan, John Kelton, Sandip P. Patel. Disparities in biomarker testing practices in patients with metastatic non-small cell lung cancer (NSCLC) 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 6122.