Primary Reference: Kerr, KM et al. Lung Cancer, April 1, 2021.
Genes: ALK, BRAF, EGFR, ERBB2/HER2, FGFR, KRAS, NRG1, NTRK, MET, RET, ROS1.
Cancer biomarker testing varies across Europe, and the field is rapidly advancing. This paper provides a comprehensive view of best practices for biomarker testing at diagnosis and during treatment for non-small cell lung cancer (NSCLC) in Europe. Lung cancer is the leading cause of cancer death in the world, and more than 80% of cases are NSCLC.
Today, biomarkers are regularly used to select first-line targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy) in NSCLC. To avoid unnecessary re-biopsies, the authors advise biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards. PD-L1 expression testing should also be done before initiating treatment with immunotherapies.
Several addictive oncogenic driver alterations have already been identified in NSCLC, including ALK, BRAF, EGFR, ERBB2/HER2, FGFR, KRAS, NRG1, NTRK, MET, RET, and ROS1. The authors write that: “The growing number of licensed and emerging therapies targeted to NSCLC genetic alterations, combined with continuously evolving molecular biology technologies, has resulted in rapid change. This is challenging for formulating and implementing guidelines for biomarker testing. Therefore, despite serving as the foundation for NSCLC precision medicine, molecular testing rates remain suboptimal.”
Recent advances have included faster screening technologies for single-driver mutations and Improvements in DNA- and RNA-based next-generation sequencing technologies that allow analysis groups of genes in a single assay. But turnaround times remain relatively long. “Consequently, rapid screening technologies are being implemented alongside next-generation sequencing,” they write.
Another challenge in NSCLC is primary and secondary resistance to targeted therapies. “…comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumor DNA may provide important information to guide second- or third-line therapies.” The authors write. Longitudinal biomarker testing can also be used to track tumor evolution and heterogeneity over disease progression.
Additional resource:
Rare deleterious germline variants and risk of lung cancer. Liu et al. Nature Precision Oncology. Feb. 16, 2021. The authors write that “Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC).” To start, they performed whole exome plus targeted sequencing of germline DNA on 1045 LC cases and 885 controls. They focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were then further validated in a series of 26,803 LCs and 555,107 controls. They identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar.
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