Advances in the treatment of lung cancer have led to the development of targeted therapy, and for patients with non–small cell lung cancer (NSCLC), tyrosine kinase inhibitors (TKIs) have improved patient outcomes and tolerability when compared with platinum-based chemotherapy. Targetable alterations in nonsquamous NSCLC included EGFR, which occurs in 10% to 15% of White patients and 40% of Asian patients; KRAS mutations, which are found in 20% to 30% of patients; ALK translocations, which occur in 3% to 7% of patients; BRAF mutations and MET amplifications, which each occur in 2% to 4% of patients; and ROS1 rearrangements, RET, and NRTK fusions, which each occur in 0.5% to 2% of patients. Alongside targeted therapies, advancements in molecular diagnostics have made routine the use of tumor molecular assessment in patients with NSCLC. The International Society for the Study of Lung Cancer and the European Society of Medical Oncology now recommend next-generation sequencing (NGS) to assess the molecular profile of patients with advanced NSCLC. This requires the use of tumor tissue, which can have limited availability due to tumor site location or sample size inadequacy.
To overcome these limitations, liquid biopsy can be performed on blood, pleural effusion, ascites, or urine to detect, analyze, or monitor cancer in a minimally invasive manner. Liquid biopsy specificity in detecting mutations in circulating tumor DNA (ctDNA) is good at 90% to 100%, but the sensitivity is only 60% to 70%. Despite these concerns, liquid biopsy may be a feasible alternative to tissue biopsy in patients with NSCLC.
A recent review analyzed the clinical utility and application of liquid biopsy for molecular profiling in patients with NSCLC. The NILE trial, which included 282 treatment-naïve patients with NSCLC, showed that as few as 18% of patients had a complete tissue analysis of biomarkers of interest, with 68.1% of patients having a partial profile. Liquid biopsy with NGS of all recommended genes, however, was performed on 95% of patients and had an 80% sensitivity and a 100% positive predictive value with a shorter turnaround time compared to tissue biopsy. For patients with early-stage NSCLC that is surgically resected, multiple studies have analyzed the use of liquid biopsy to help identify patients who have an increase in ctDNA during adjuvant chemotherapy who may need careful evaluation. In patients with advanced NSCLC, liquid biopsy has been studied in relation to tumor mutational burden and immunotherapy, but the results across the studies have been conflicting. However, cell-free DNA has emerged as a biomarker of immunotherapy response. ctDNA evaluation has been validated for the assessment of EGFR mutational status, the detection of T790M mutation, and monitoring during TKI treatment in treatment-naïve patients with advanced or metastatic NSCLC. Investigations in ALK rearrangements have found liquid biopsy to be promising but with a lower sensitivity compared with EGFR mutation. Studies on the application of liquid biopsy for other common NSCLC mutations are ongoing to determine its use in NSCLC management.
Source: Nigro MC, Marchese PV, Deiana C, et al. Clinical utility and application of liquid biopsy genotyping in lung cancer: a comprehensive review. Lung Cancer (Auckl). 2023;14:11-25.