Detection of plasma EGFR mutations for personalized treatment of lung cancer patients without pathologic diagnosis

Abstract

Introduction Next‐generation sequencing (NGS) and digital polymerase chain reaction (PCR) based platforms have been used to detect EGFR mutations in plasma circulating tumor DNA (ctDNA) with high accuracy. Generally, molecular testing is performed after histopathological analysis. However, many patients with suspected advanced nonsmall cell lung cancer are unable to undergo biopsy thus forgoing potential treatment with highly effective tyrosine kinase inhibitors (TKIs) in patients with sensitizing EGFR mutations. We examined the utility of ctDNA testing to detect EGFR mutations in patients' plasma, where tissue biopsy is not feasible. Methods We conducted a single‐center, prospective study of 30 Chinese patients with suspected advanced lung cancer, who were unable to undergo a biopsy for initial diagnosis due to comorbidities or poor performance status. Patients with plasma EGFR sensitizing mutations were treated with first‐generation EGFR TKIs. Results Twenty of 30 patients enrolled had sensitizing EGFR mutations in ctDNA and were started on EGFR TKIs. After a median follow‐up of 12 months, median progression‐free survival (PFS) was 10 months and median overall survival (OS) was not reached. The median OS for the 10 untreated patients was 3 months. Conclusions In our study, patients with plasma EGFR mutations treated with TKIs showed disease control rate (DCR) and PFS similar to historical controls that were treated based on tissue testing. This is the first prospective study showing that ctDNA genotyping provides a feasible diagnostic approach for frail lung cancer patients who are unable to undergo biopsy, which subsequently leads to EGFR‐targeted therapy, and improved outcomes in this subgroup of patients.

Management of Lung Cancer During the COVID-19 Pandemic

“…9 Although tissue diagnosis is still the gold standard for diagnosis of lung cancer, if resources are extremely limited, use of plasma-based genotyping to direct therapeutic care may be considered, especially if a driver mutation is detected for certain phenotypes (eg, neversmoker, Asian, female) and the radiographic features of lung cancer are thought to be unequivocal (eg, spiculated lung mass). 10…”

“…49 Interventions that alleviate severe symptoms should remain a high priority. When using palliative radiotherapy, hypofractionation should be the considered with single-fraction regimens for bone metastases (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) Gy in 1 fraction) and spinal cord compression or 2-fraction regimens for airway obstruction (17 Gy in 2 fractions). 50 Bone-modifying treatments (IV bisphosphonates or denosumab) can be deferred in patients without hypercalcemia or active symptomatic bone invasion.…”

Lung cancer management in the COVID-19 pandemic

“…asla sigara içmeyen, Asyalı, kadın) ve akciğer kanserinin radyografik özelliklerinin kesin olduğu dü-şünülen durumlarda tedavi açısından değerlendirilmelidir. (örn; spiküle akciğer kitlesi ) (10) . (11) .…”

Clinical Utility of Plasma Cell-Free DNA EGFR Mutation Analysis in Treatment-Naïve Stage IV Non-Small Cell Lung Cancer Patients

“…Traditionally, molecular genotyping has been performed using tissues, but with recent technical advances, various liquid biopsy platforms can now be used to detect plasma-circulating tumor deoxyribonucleic acid (DNA) [6,8]. Comprehensive cell-free DNA (cfDNA) analysis has the advantages of a faster turnaround time (TAT) than tissue analysis, less invasiveness, and the ability to obtain genetic information when tissue biopsy is not possible [9][10][11].…”