We have witnessed immense progress for lung cancer, such as screening, minimally invasive techniques for diagnosis and most important personalised customised treatment, in particular, the advances in new targeted therapies and new immunotherapies. These new treatments are reflected in the improved survival rates for patients. Next Generation Sequencing and Precision Oncology tools have been at the centre of this progress due to significant decoding of disease at the molecular genomic level.
Genetic Molecular Biomarker testing for somatic, disease-associated variants/mutations is recommended before starting therapy in eligible patients because targeted therapy has been shown to decrease tumour burden, decrease symptoms, and dramatically improve the quality of life for patients with specific somatic genomic alterations. Molecular testing is used to test for oncogenic genomic driver events for which targeted therapies are available.
It is important to note that several different tests may be used to identify the same biomarker, including FDA-approved biomarker tests and validated laboratory tests and biomarker testing is rapidly changing and improving. NCCN also recommends upfront testing for PD-L1, which is an immune biomarker to assess whether patients are candidates for immune checkpoint inhibitors (ICIs). Single-agent targeted therapy is recommended for patients with actionable driver mutations (i.e., ALK fusion, EGFR activating mutations, METex14 skipping, NTRK1/2/3 fusions, RET rearrangements, ROS1 rearrangements) or those with emerging driver mutations. Chemotherapy/immunotherapy regimens are recommended for patients without targetable somatic variants/mutations.
Next generation sequencing (NGS) is a type of broad molecular profiling laboratory system that can in parallel (rather than the previous sequential molecular tests) detect panels of mutations and gene fusions if the NGS platforms have been designed and validated to detect these somatic genomic alterations. It is important to recognize that NGS requires quality control as much as any other diagnostic technique; because it is design dependent, the panel of genes and abnormalities detected with NGS will vary depending on the design of the NGS platform. For example, some NGS platforms can detect both mutations and gene fusions, as well as copy number variation, but they are not uniformly present in all NGS assays being conducted either commercially or in institutional laboratories. The clinicians are astutely aware of these nuances and choose wisely to curate ideal laboratory work up and plan treatment in the patient's best interest.
(Author credits: Dr. Kirti Chadha, Chief Scientific Officer, Metropolis Healthcare Limited)
