The evolving landscape of biomarker testing for non-small cell lung cancer in Europe

Abstract

The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by smallmolecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment.Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for singledriver mutations have been implemented. Improvements in DNA-and RNA-based next-generation sequencing

Afatinib in EGFR TKI-Naïve Patients with Locally Advanced or Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase IIIb Studies

“…Of note, the constituent studies in this analysis were largely undertaken before osimertinib was widely available as a second-line treatment option in patients with T790M-mediated acquired resistance to EGFR TKIs. Therefore, as it is estimated that 50–70% of patients treated with afatinib acquire the T790M mutation ( 24 ), the observation of widespread treatment beyond progression in this study probably does not reflect contemporary treatment practices, especially as tumor re-biopsies at the point of radiological progression are becoming more commonplace ( 25 ). In patients who acquire the T790M mutation, treatment with osimertinib should not be delayed.…”

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

“…KRAS can be detected through numerous procedures including PCR, Sanger sequencing or next-generation sequencing from tissue or liquid biopsy [60,61]. However, testing is currently often confined to clinical trials or academic institutions, and biomarker testing algorithms vary according to country and regional guidelines (reviewed in Kerr et al [62]). In terms of liquid biopsy testing, non-tumor derived mutations that expand during clonal hematopoiesis are an important consideration as they can cause false positives if the results are misinterpreted [63,64].…”

Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review

“…The identification of a targetable mutation implies the possibility to treat the patient with a more effective therapy than conventional cytotoxic chemotherapy [ 20 , 21 ]. As our knowledge of rarer mutations increases and new drugs become available, guidelines suggest testing an increasing number of them [ 17 , 20 , 22 , 23 , 24 ]. Most current guidelines recommend testing for at least epidermal growth factor receptor (EGFR) mutations, v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation, neurotrophic receptor tyrosine kinase (NTRK) gene fusions, and anaplastic lymphoma kinase (ALK) and ROS1 rearrangements, in addition to immunohistochemical evaluation of the programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) [ 6 , 11 , 12 , 13 , 17 , 20 , 25 , 26 ].…”