Inside Diagnostics New ESMO clinical practice guidelines
The new ESMO clinical practice guidelines are now published and clarify the position of liquid biopsies in the testing algorithm for Stage IIIB-IV lung carcinoma with EGFR activating mutations. Liquid biopsy samples are a surrogate source of tumour DNA for mutation testing. The authors further explain that a positive result of a well validated test allows for treatment decision with a third generation tki, but in case of negative results a tissue biopsy should be attempted to find undetected additional T790M mutation positives.
Primary lung cancer is the most common malignancy after non-melanocytic skin cancer, and the leading cause of human cancer deaths worldwide. These guidelines focus on diagnosis and personalised medicine, staging and risk assessment and management of advanced/metastatic NSCLC including follow-up.
The majority of patients will progress after 9–12 months of treatment with an EGFR TKI, and various mechanisms of acquired resistance to first-generation EGFR TKIs have been described. The most common (49%–60%) mechanism of acquired resistance is the acquisition of a single recurrent missense mutation within exon 20, the T790M mutation. This mutation leads to the substitution of threonine by methionine at position 790, which encodes part of the kinase domain of the receptor and results in increased affinity for ATP, causing resistance to competitive inhibition by reversible EGFR TKIs such as gefitinib and erlotinib.
A valid alternative to tissue rebiopsy is represented by liquid biopsy, which has been validated, represents a surrogate source of DNA and is a new strategy for tumour genotyping, mainly at the time of progression for EGFR-mutated patients [III, A]. In the event that a T790M mutation in peripheral blood is observed, treatment with third-generation EGFR TKIs is justified. If a T790M-negative liquid biopsy is observed, a tissue rebiopsy is recommended if feasible and if accepted by the patient.
Diagnostics Manager AstraZeneca
NS ID 1014231 Approval Date 10/2016
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About the Author
Rudy Hovelinck obtained a scientific degree first in biochemistry at Ghent University and later in Molecular Biology at the ULB. Initially exploring the academic world in diverse fields as genetics, protein chemistry and virology, he soon realised that bridging scientific knowledge to the medical world was a more meaningful way of spending his professional life. This journey started in the field of pathology biomarker testing, introducing HER2 IHC and ISH testing for patient therapy selection and continued in the field of molecular oncology. Today at AstraZeneca he works as a diagnostics manager. In this role he is passionately contributing to the successful introduction of novel biomarkers and support current testing strategies for patient selection. In his own time he enjoys travelling with his family exploring the world and spending time close to nature. Specialties: Oncology, Anatomic Pathology, Biomarker Development, Medical Devices.