Consensus Recommendations to Optimize Testing for New Targetable Alterations in Non-Small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) has historically been associated with a poor prognosis and low 5-year survival, but the use of targeted therapies in NSCLC has improved patient outcomes over the past 10 years. The pace of development of new targeted therapies is accelerating, with the associated need for molecular testing of new targetable alterations. As the complexity of biomarker testing in NSCLC increases, there is a need for guidance on how to manage the fluid standard-of-care in NSCLC, identify pragmatic molecular testing requirements, and optimize result reporting. An expert multidisciplinary working group with representation from medical oncology, pathology, and clinical genetics convened via virtual meetings to create consensus recommendations for testing of new targetable alterations in NSCLC. The importance of accurate and timely testing of all targetable alterations to optimize disease management using targeted therapies was emphasized by the working group. Therefore, the panel of experts recommends that all targetable alterations be tested reflexively at NSCLC diagnosis as part of a comprehensive panel, using methods that can detect all relevant targetable alterations. In addition, comprehensive biomarker testing should be performed at the request of the treating clinician upon development of resistance to targeted therapy. The expert multidisciplinary working group also made recommendations for reporting to improve clarity and ease of interpretation of results by treating clinicians and to accommodate the rapid evolution in clinical actionability of these alterations. Molecular testing of all targetable alterations in NSCLC is the key for treatment decision-making and access to new therapies. These consensus recommendations are intended as a guide to further optimize molecular testing of new targetable alterations.

Biomarker Turnaround Times and Impact on Treatment Decisions in Patients with Advanced Non-Small Cell Lung Carcinoma at a Large Canadian Community Hospital with an Affiliated Regional Cancer Centre

“…Another study where biomarker testing was conducted off-site reported a shorter pre-laboratory time of 3 business days [ 10 ]. According to the College of American Pathologists and Canadian consensus recommendations, the tissue should be received for molecular testing within 3 working days from diagnosis to avoid delays in biomarker testing [ 3 , 14 ]. The internal handling of tissue and variability in transportation time were cited as sources of delay in pre-laboratory time [ 18 , 19 ].…”

Case report: olaparib use in metastatic lung adenocarcinoma withBRCA2pathogenic variant

“…The amplicon-based approach relies on primers that flank the interest of sequencing. This can lead to false negatives because of allele dropout or genomic deletions (Ionescu et al 2022). A study showed that amplicon-based assays had a lower rate of detecting gene fusions in NSCLC patients when compared to hybrid capture-based assays (Heydt et al 2021).…”

Guidance for clinicians and patients with non-small cell lung cancer in the time of precision medicine

“…In metastatic aNSCLC, it is vital to establish the correct histologic subtype and conduct comprehensive, parallel NGS at the time of initial diagnosis as there are a number of genomic alterations, each of which requires an associated molecular targeted therapy (Table 1) (4)(5)(6)(7)(8)12). NGS with an appropriate fusion panel enables simultaneous detection of all existing biomarkers/alterations in any number of genes at any given timepoint and can detect rare molecular alterations with low prevalence/frequency (≤1%) (17) in samples with 20% or less malignant cells (12,17), as recommended by experts (11).…”

“…One limitation introduced by NGS is the difficulty in prioritizing drivers for targeted therapy when multiple drivers are present (31). A list of some commercially available NGS panels for aNSCLC testing can be found in reviews by Cainap et al (38) and Ionescu et al (5).…”