Idylla for lung cancer

Lung cancer is the most common cancer worldwide, contributing for 13% of all cancer types. 85% of lung cancers are non-small cell lung cancers (NSCLC), of which histologically adenocarcinoma is the most prevalent.

EGFR mutations in exons 18-21 have been associated with sensitivity and resistance to a number of targeted anti-cancer therapeutics and testing is recommended in all patients with advanced NSCLC of a nonsquamous subtype.1  2  Exon 19 deletion and exon 21 (L858R, L861Q), exon 18 (G719X), and exon 20 (S768I) mutations are associated with sensitivity to EGFR tyrosine kinase inhibitors (TKI’s) whereas exon 20 insertion mutations may predict resistance to TKI’s. EGFR T790M mutation is the main cause of acquired resistance to TKI therapy and has been reported in about 55% of patients with disease progression after initial response to 1st or 2nd generation TKI’s.3  4  Prevalence of EGFR mutations in NSCLC adenocarcinomas is 10-15% in Western and up to 50% in Asian patients.5

Gene fusions represent an important class of gene rearrangements and have become important in NSCLC, as they are linked to responses to certain targeted therapies. Their accurate and fast detection is critical to guide therapy choices, which is the reason why testing for gene rearrangements such as gene fusions is included in international NSCLC testing guidelines (including ESMO and NCCN).

However, comprehensive testing of actionable gene rearrangements in NSCLC are often complex and can require different technologies.6 In order to test all needed biomarkers, laboratories usually have to use different instruments which are often not available within their own lab. Using different instruments also requires having enough biopsy samples of sufficient good quality, which can be difficult to obtain, especially in NSCLC patients.

• 1National Comprehensive Cancer Network website. NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer Version 6. 2017. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed August 2018
• 2Novello S. et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2016) 27 (suppl 5): v1-v27; Accessed August 2018
• 3National Comprehensive Cancer Network website. NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer Version 6. 2017. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed August 2018
• 4Novello S. et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2016) 27 (suppl 5): v1-v27; Accessed August 2018
• 5Cooper WA et al. J Thorac Dis 2013; 5 (S5): S479-490. Molecular Biology of lung cancer
• 6I.e. gene fusions and METex14 skipping. Techniques used to detect NTRK gene fusions include DNA-based next-generation sequencing (NGS), RNA-based NGS, reverse-transcriptase PCR (RT-PCR), fluorescence in situ hybridisation (FISH), and immunohistochemistry (IHC). Source: OncologyPro, ESMO, last consulted on 2 June 2022: https://oncologypro.esmo.org/oncology-in-practice/anti-cancer-agents-an…