Rapidly Evolving Landscape for Biomarker Testing in NSCLC Prompts Updated European Recommendations

Lung cancer is one of the most common and leading causes of cancer deaths worldwide. More than 1.7 million people died from the disease in 2018.¹ Non–small-cell lung cancer (NSCLC) accounts for the majority (~84%) of these cases.¹ With the advent of precision medicine, the treatment landscape for NSCLC is rapidly evolving from traditional chemotherapy to personalized medicine, which has improved treatment outcomes and improved quality of life for patients with NSCLC.¹ Knowledge of disease pathways, the development of drugs to block these pathways, and technology to detect genetic mutations leading to NSCLC have led to targeted drug therapies.¹ Biomarkers have been identified, and continue to emerge, which help to screen for targeted NSCLC therapy.² In a review article published in Lung Cancer in February 2021, the evolving landscape of biomarker testing for NSCLC in Europe was presented.²

Research has demonstrated there are population differences in the frequency of oncogenic driver mutations. For example, in Asia EGFR mutations are more frequent than KRAS mutations, which are more frequently found in Europe. Biomarker testing guidelines also vary by country. International consensus guideline recommendations are to test for EGFR, BRAF, ALK, and ROS1 in advanced NSCLC.² The European Society for Medical Oncology (ESMO), the National Comprehensive Cancer Network, and Pan-Asian NSCLC guidelines also recommend PD-L1 testing.² ESMO recommends next-generation sequencing (NGS) in nonsquamous NSCLC and the use of large multigene panels if it is cost-effective.² International guidelines are generally taken into account when national guidelines are being developed.

Due to the rapid development of new molecular testing technologies, there is generally a lag in development of new guidelines, which may be a barrier in reimbursement and uptake of biomarker testing in routine clinical practice. Organizational barriers include resource scarcity, and regulatory agencies are additional barriers to biomarker testing uptake. Turnaround time, laboratory challenges, and tissue biopsy constraints were also cited as barriers. A lack of current training in genomics may lead clinicians to feel less confident about interpreting results for clinical care. In addition, the rapid development of new biomarkers makes standardization of the reporting and interpretation of genomics data a challenge.

To assist in overcoming the challenges around biomarker testing and interpretation, the following best practices were put forth.² A multidisciplinary management approach to provide complete staging and better adherence to guidelines generally results in improved patient survival. Obtaining appropriate tissue samples for testing utilizing a multidisciplinary approach is also recommended. Various healthcare professionals using a variety of tissue sampling techniques is recommended to collect tissue and liquid biopsies at appropriate stages and in sufficient numbers depending on tumor type. NGS adoption into routine practice at the time of diagnosis is also recommended. Finally, external quality assessment programs to assess laboratory quality control and internal validation procedures is beneficial clinically and improves reporting.

Current best practice recommendations for the diagnosis and management of patients with newly diagnosed advanced NSCLC and progressive or recurrent NSCLC and new and emerging targeted therapies for NSCLC, technological developments, and European legislative changes were also presented in this review.

References

1. Yuan M, Huang LL, Chen JH, et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019;4:61.
2. Kerr KM, Bibeau F, Thunnissen E, et al. The evolving landscape of biomarker testing for non-small cell lung cancer in Europe. Lung Cancer. 2021;154:161-175.