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Studies confirm benefit of plasma genotyping to predict treatment benefit in patients with non-small-cell lung cancer

The benefit of plasma genotyping to predict treatment benefit in patients with non-small-cell lung cancer (NSCLC) is confirmed in three studies presented at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.1 Researchers however warned that plasma tests are unlikely to fully replace tissue biopsies.

Patients with NSCLC are tested for epidermal growth factor receptor (EGFR) mutations which indicate their suitability for targeted EGFR tyrosine kinase inhibitor (TKI) therapy. Tissue biopsies are the gold standard but are not possible in around 20% of NSCLC patients. Plasma is a potential alternative for EGFR mutation analysis through extraction of circulating tumour DNA (ctDNA).

The primary results of the ASSESS trial, presented at ELCC 20152, demonstrated that ctDNA is suitable and feasible for EGFR mutation analysis in real-world practice. The analysis presented today examined whether patient disease or demographic characteristics influenced the detection of EGFR mutations in plasma. There was increased sensitivity of EGFR mutation detection in plasma associated with increasing number and severity of metastases. EGFR mutation detection in plasma was also significantly higher in patients aged less than 65 years old compared with older patients. These findings were independently confirmed by the companion IGNITE study.

“Further studies are required to confirm these findings and identify potential underlying biological mechanisms – the age finding in particular is interesting,” said Dr Nicola Normanno, chief of the Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, Naples, Italy, author of one of the studies. “The increased ability to detect EGFR mutations in plasma from patients with a higher number of organs with metastases makes sense biologically, as these patients have higher tumour burden and we could expect more ctDNA to be released in the blood. The same could also be true for patients that have metastases to organs further away from the lungs (M1b).”

He continued: “The link with age is more difficult to understand. Evidence suggests that the biological features of certain tumours change with age. However, the specific biological mechanisms underlying the correlation between the success of plasma analysis and age will need to be investigated further.”

Commenting on the implications of the findings for clinical practice, Normanno said: “If plasma testing is more reliable for some patients with certain characteristics, this may have implications in the way that we conduct mutation testing for patients with NSCLC, and ultimately impact upon treatment decisions. Our data suggests that for the majority of patients with metastatic disease a plasma test could be sufficient to determine EGFR mutation status particularly when a robust and reliable methodology is used. Due to the low sensitivity of plasma genotyping (60-70%), a biopsy will still be recommended in plasma negative cases.”