This page was created by the Value Proposition Working Group to support the Working Group’s key messages about the value of biomarker testing in non-small cell lung cancer (NSCLC).
Advancing Patient Care Through Biomarker Testing in NSCLC
Applying precision medicine solutions at an institutional level leads to the best possible patient outcomes by ensuring that each patient receives the right treatment at the right time. Precision medicine and biomarker testing implemented at diagnosis can equip oncology providers with the data necessary to personalize patient care and help patients avoid treatments that are unlikely to work, exposing them to unwanted toxicity.
Evolving clinical guidelines for many solid tumors recommend that when feasible, testing be performed via a broad, multi-gene next-generation sequencing (NGS) tests to support physicians in identifying therapies and clinical trial options specific to each individual patient and their disease. Broad or comprehensive NGS testing, also referred to as molecular testing, comprehensive biomarker testing, genomic profiling, and genotyping, simultaneously assesses tissue or blood samples for all potentially actionable genomic variants (biomarkers) in a single test.
Clinical Guidelines on Biomarker Testing
Ensure your institution is providing state-of-the-art cancer care that aligns with evolving nationally recommended guidelines*:
- National Comprehensive Cancer Network® (NCCN®) NSCLC Guidelines
- American Society of Clinical Oncology (ASCO) Guidelines
- Associate for Molecular Pathology (AMP) / College of American Pathologists (CAP) / International Association for the Study of Lung Cancer (IASLC) Guidelines [link to URL to come]
*Clinical guidelines may require account credentials to access.
- Learn more about the importance of advancing patient care through biomarker testing
A global analysis of the value of precision medicine in oncology: the case of non-small cell lung cancer
In this study, the authors assessed the value of biomarker testing and use of precision medicine for advanced NSCLC in multiple countries by comparing 1-year and 5-year survival model results of different testing scenarios:
- No biomarker testing (chemotherapy for all)
- Sequential testing (EGFR and ALK, followed by targeted therapy or chemotherapy)
- Next-generation sequencing (NGS) “multigene testing” (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, and PD-L1, followed by targeted or immunotherapy)
Use of upfront biomarker testing led to an increase in patient survival rates when compared to no testing, with a near doubling of the progression-free disease phase with NGS, and a decrease in the number of treatment-related adverse events.
Association between availability of molecular genotyping results and overall survival in patients with advanced nonsquamous non-small-cell lung cancer
In this real-world cohort study, the authors examined electronic health records of 326 patients with newly diagnosed metastatic nonsquamous NSCLC to determine the association between the availability of biomarker testing before initiating therapy and overall survival.
At a 14.2-month median follow-up, patients with biomarker testing results available prior to first-line therapy had significantly longer overall survival rates than patients who did not have results available.
Improving biomarker testing in advanced non-small-cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA
In this study, the authors compared biomarker testing practices between OneOnc community oncology network and other nationwide sites. NGS testing rates were higher in the OneOnc network, reflecting the success of educational, pathway, and operational initiatives. Additionally, patients who received NGS testing had a greater likelihood of receiving targeted treatment than patients who received non-NGS testing (eg, fluorescence in situ hybridization, immunohistochemistry, or polymerase chain reaction testing) or individual biomarker testing (testing for each biomarker one at a time).
However, opportunities remain to optimize personalized healthcare by increasing NGS uptake, shortening turnaround times, and reducing the number of patients who start treatment before receiving complete biomarker test results.
Biomarker testing, treatment, and outcomes in patients with advanced/metastatic non-small cell lung cancer using a real-world database
In this study, the authors compared overall survival rates by biomarker testing status and by receipt of guideline-recommended therapy in a large cohort of US patients with advanced or metastatic NSCLC. Despite recommendations from nationally recognized clinical guidelines, the overall rate of testing for actionable biomarkers was low. Of 21,572 patients studied, only 69% received testing for at least 1 actionable biomarker prior to or on initiation of first-line treatment, demonstrating opportunity for improvement.
Patients who received front-line biomarker testing and appropriate guideline-recommended therapy experienced significant improvements in overall survival rates compared with those who never received biomarker testing.
Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer
Despite improved insurance coverage since 2018, comprehensive biomarker testing remains substantially underutilized.
In this real-world, electronic health record study, the authors examined the implications of timely comprehensive biomarker testing on quality-of-care for patients with advanced NSCLC.
Use of profiling results to inform first-line therapy choice was associated with increased use of matched targeted therapies, translating into longer time to therapy discontinuation and avoidance of costly treatments that are unlikely to be effective.
References
- Aggarwal C, et al. Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. JCO Precis Oncol. 2023 Jul;7:e2300191. doi: 10.1200/PO.23.00191.
- Bhandari NR, et al. Biomarker testing, treatment, and outcomes in patients with advanced/metastatic non-small cell lung cancer using a real-world database. J Natl Compr Canc Netw. 2023 Sep;21(9):934-944.e1. doi: 10.60 04/jnccn.2023.7039.
- Hofmarcher T, et al. A global analysis of the value of precision medicine in oncology – The case of non-small cell lung cancer. Front Med (Lausanne). 2023 Feb 20:10:1119506. doi: 10.3389/fmed.2023.1119506.
- Schwartzberg L, et al. Improving biomarker testing in advanced non-small-cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA. Future Oncol. 2023 Jun;19(20):1397-1414. doi: 10.2217/fon-2022-1216.
- Yorio J, et al. Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer. JCO Precis Oncol. 2024 Mar;8:e2300292. doi: 10.1200/PO.23.00292.
Providing Accessible and Equitable Biomarker Testing for NSCLC
Implementing precision medicine will enhance accessibility and equity to testing and appropriate treatments for all patients. Comprehensive biomarker testing for all patients with NSCLC can help to reduce existing disparities in care and improve clinical outcomes, quality of care, and patient satisfaction.
A precision medicine approach can be customized to fit your patients, care teams, and framework, with solutions that align with existing workflows and show immediate positive impact.
- Learn more about the importance of providing accessible and equitable biomarker testing for NSCLC
Healthcare disparities, screening, and molecular testing in the changing landscape of non–small cell lung cancer in the United States: a review
In this review article, the authors describe the disparities that exist across lung cancer screening, diagnosis, and treatment regimens; impact on incidence and survival; and demographic variances. Several strategies to reduce lung cancer health disparities are reviewed including improving screening rates, increasing clinical trial diversity, and implementing standardized molecular testing policies.
Solutions are presented to address potential difficulties that may be encountered in establishing biomarker testing programs, and include:
- Strategic use of liquid biopsy testing (cfDNA)
- Increased education opportunities for physicians to stay abreast of rapidly evolving practice standards and treatments
- Identification and support of a champion physician to educate healthcare teams
- Inclusion of nurse navigators to facilitate communication within care teams and support patient education
- Collaboration with patient advocacy organizations to disseminate information
- Familiarization with CMS coverage determinations on next-generation sequencing (NGS) as a diagnostic tool
- Support participation of underserved populations in clinical trials
Disparities in biomarker testing and clinical trial enrollment among patients with lung, breast, or colorectal cancers in the United States
In this study, the authors examined racial differences in biomarker testing and clinical trial participation in the United States among patients with advanced/metastatic NSCLC, colorectal cancer, or breast cancer.
Among nearly 15,000 patients with NSCLC, Black patients were significantly less likely than White patients to receive NGS testing at any time (39.8% vs 50.1%) or to be treated in a clinical trial (1.9% vs 3.9%).
As NGS testing for patients with advanced NSCLC is fundamental to determining effective therapies, this study underscores the substantial disparity in equitable access to appropriate care.
Racial and ethnic inequities at the practice and physician levels in timely next-generation sequencing for patients with advanced non–small-cell lung cancer treated in the US community setting
In this study, the authors examined racial and ethnic disparities in rates of NGS for patients with advanced NSCLC in a community setting to inform policies to improve equitable quality of care. They reported that among ~12,000 patients with advanced NSCLC, non-Latinx Black and Latinx patients were consistently underserved, with ~8% lower rate of NGS testing versus non-Latinx White.
Based on these findings, there is a health equity barrier in biomarker testing, with Latinx (and potentially other minorities) are being underrepresented in biomarker testing compared to non-Latinx White individuals.
References
- Bruno DS, et al. Disparities in Biomarker Testing and Clinical Trial Enrollment Among Patients With Lung, Breast, or Colorectal Cancers in the United States. JCO Precis Oncol. 2022 Jun:6:e2100427. doi: 10.1200/PO.21.00427.
- Kurzrock R, et al. Healthcare disparities, screening, and molecular testing in the changing landscape of non–small cell lung cancer in the United States: a review. Cancer Metastasis Rev. 2024 May 16. doi: 10.1007/s10555-024-10187-6. Online ahead of print.
- Vidal GA, et al. Racial and Ethnic Inequities at the Practice and Physician Levels in Timely Next-Generation Sequencing for Patients With Advanced Non–Small-Cell Lung Cancer Treated in the US Community Setting. JCO Oncol Pract. 2024 Mar;20(3):370-377. doi: 10.1200/OP.23.00253. Epub 2024 Jan 9.
Operational Improvements to Enhance Biomarker Testing in NSCLC
Use of precision medicine can drive substantial cost savings for your organization by enabling more effective treatments, reducing unnecessary interventions, and improving patient outcomes.
Integrating timely use of comprehensive biomarker testing, employing standardized and streamlined clinical workflows such as "reflex" biomarker testing, and establishing support infrastructure across relevant cancers, can help reduce patient time to treatment. Additional efficiencies and improvements in outcomes can be found from better educating physicians in precision medicine and facilitating precision-medicine enabled multidisciplinary treatment approaches.
- Learn more about operational improvements to enhance biomarker testing in NSCLC
Electronic medical record–based nudge intervention to increase comprehensive molecular genotyping in patients with metastatic non–small cell lung cancer: results from a prospective clinical trial
In this publication, the authors describe how they designed, implemented, and assessed performance of an electronic medical record (EMR)-based “nudge intervention” to prompt plasma-based molecular testing (ie, liquid biopsy) at the time of initial medical oncology consultation for patients with newly diagnosis NSCLC.
Across three practice sites in a large health system, the EMR “nudge intervention” lead to a significantly higher percentage of patients who received concurrent plasma and tissue comprehensive biomarker testing at diagnosis (68.4% before the EMR nudge integration to 93.6% following the nudge) and guideline-concordant care (78.2% before the EMR nudge integration to 89.8% following the nudge).
Interpreting and integrating genomic tests results in clinical cancer care: overview and practical guidance
In this review publication, the authors provide a primer on the use of precision medicine and opportunities for enhanced treatment through next-generation sequencing (NGS) testing in oncology. They assert that a lack of understanding of the clinical utility of NGS and difficulty of results interpretation by practicing oncologists result in decreased use of precision medicine in routine cancer care.
The authors present practical guidance for interpreting genomic test results to help inform clinical decision-making and discuss potential challenges to wider implementation of precision medicine into routine care.
Pathologist-initiated reflex testing for biomarkers in non-small-cell lung cancer: expert consensus on the rationale and considerations for implementation
In this publication, the authors provide an expert consensus review of the importance of implementing reflex testing in NSCLC, in which the responsibility for comprehensive molecular testing for an agreed range of biomarkers lies with the pathologist versus the treating oncologist.
The study’s authors demonstrate how reflex testing has been shown to standardize and expedite the process of ordering biomarker tests to ensure more patients are tested and provide considerations for defining reflex testing protocol, engaging with institutional stakeholders, and defining roles and responsibilities within the multi-disciplinary care team.
Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma
In this small, single-institution study, researchers evaluated the impact of standardized reflex molecular testing, in which the pathologist orders a group of pre-approved biomarkers at the time of initial diagnosis, for patients with newly diagnosed NSCLC. The authors reported that average turnaround time for test results was significantly reduced by 37 days with reflex testing and resulted in a higher variant detection rate than standard molecular biomarker ordering practices over a 2-year timeframe.
The authors identified adoption of reflex ordering practices by physicians across sites and utilization of the institution laboratory for analyses versus an unaffiliated laboratory as contributors to improved turnaround time for testing results.
Closing the testing gap: standardization of comprehensive biomarker testing for metastatic non-small-cell lung cancer in a large community oncology practice
In this study, the authors evaluated the feasibility and impact of implementing a guideline-concordant comprehensive biomarker testing program for all newly diagnosed patients with metastatic NSCLC within a large community practice. The implementation process included provider education, initial electronic health record consult notes, and accompanying order sets, with further adjustments made after an initial evaluation trial.
The study authors reported a 1-year increase in testing rates from 68% to 92.7% and demonstrated the feasibility of a standardized workflow for comprehensive biomarker testing within a multisite community-based practice.
Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer
In this study, researchers aimed to assess the total cost associated with next-generation sequencing versus polymerase chain reaction (PCR) testing strategies, which often involve analyzing single or pre-selected biomarkers that may not align with clinical guideline recommendations, among patients with metastatic NSCLC from a Medicare and Commercial payer perspective. Analysis was based on a hypothetical plan of 1 million patients insured through a blend of Medicare and commercial health plans.
NGS was associated with a shorter estimated mean time to initiation of appropriate targeted therapy compared to all other PCR strategies and resulted in the lowest per patient total cost of testing, demonstrating the clinical and economic value of adopting NGS for patients with metastatic NSCLC.
References
- Anand K, et al. Clinical Utility of Reflex Ordered Testing for Molecular Biomarkers in Lung Adenocarcinoma. Clin Lung Cancer. 2020 Sep;21(5):437-442. doi: 10.1016/j.cllc.2020.05.007. Epub 2020 May 13.
- Casolino R, et al. Interpreting and integrating genomic tests results in clinical cancer care: Overview and practical guidance. CA Cancer J Clin. 2024 May-Jun;74(3):264-285. doi: 10.3322/caac.21825. Epub 2024 Jan 4.
- Gosney JR, et al. Pathologist-initiated reflex testing for biomarkers in non-small-cell lung cancer: expert consensus on the rationale and considerations for implementation. ESMO Open. 2023 Aug;8(4):101587. doi: 10.1016/j.esmoop.2023.101587. Epub 2023 Jun 23.
- Marmarelis ME, et al. Electronic Medical Record–Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non–Small Cell Lung Cancer: Results From a Prospective Clinical Trial. JCO Oncol Pract. 2024 Jul 3:OP2400070. doi: 10.1200/OP.24.00070. Online ahead of print.
- Vanderpoel J, et al. Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer. J Med Econ. 2022 Jan-Dec;25(1):457-468. doi: 10.1080/13696998.2022.2053403
- Waterhouse DM, et al. Closing the testing gap: Standardization of comprehensive biomarker testing for metastatic non-small-cell lung cancer in a large community oncology practice. JCO Oncol Pract. 2023 Jun;19(6):e951-e956. doi: 10.1200/OP.22.00817. Epub 2023 May 1.