Effect of icotinib on advanced lung adenocarcinoma patients with sensitive EGFR mutation detected in ctDNA by ddPCR

Abstract

Background: Whether or not EGFR mutation status detected by ddPCR in plasma predicts the effect of icotinib on patients with advanced lung adenocarcinoma was determined.Methods: Plasma and matched tissue specimens from patients with advanced lung adenocarcinoma were collected prior to icotinib treatment. The ARMS method was used to detect EGFR mutation status in DNA extracted from tissue specimens, while the EGFR mutation status in ctDNA extracted from plasma specimens was determined by ddPCR. The therapeutic effects of icotinib were compared between patients with EGFRactivating mutations detected by ddPCR in ctDNA and ARMS in tissue DNA.Results: EGFR mutation status was detected in 96 tissue and 100 plasma specimens. The sensitivity and positive predictive value of 19del detected in ctDNA by ddPCR was 70.97% (22/31) and 44.90% (22/49), respectively. The positive predictive value was 84.62% (22/26) and the sensitivity was 53.66% (22/41) for the L858R mutation. For the common sensitive EGFR mutations, ddPCR had a positive predictive value of 77.19% (44/57) and a sensitivity of 48.89% (44/90). Patients with sensitive EGFR mutations in ctDNA had objective response and disease control rates (DCR) similar to patients who had sensitive EGFR mutations in tissues detected by ARMS when treated with icotinib (57.14% vs. 51.51% and 92.86% vs. 90.91%, respectively).Conclusions: Patients with sensitive EGFR mutations in plasma specimens detected with ddPCR had a higher ORR and DCR compared with patients with sensitive EGFR mutations in tissue detected with the ARMS method.

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

“…Accurate molecular typing is the basis of this precise treatment; however, qualified tumor tissue specimens cannot be obtained from every patient, so liquid biopsy was developed. Many studies have prospectively verified the high specificity (92–100%) and positive predictive value (94.0–98.6%) of ctDNA-based EGFR mutation detection using tissues as a reference [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], and these two metrics have also been consistent in guiding the targeted therapy of NSCLC [ 30 , 31 , 34 , 35 ]. Recently, research on ctDNA-based next-generation sequencing (NGS) has demonstrated potential clinical utility [ 36 , 37 , 38 , 39 ].…”

“…Table 1 presents data on the association between plasma ctDNA/cfDNA EGFR mutations and the efficacy and prognosis of targeted therapy in NSCLC patients [ 28 , 30 , 31 , 32 , 33 , 34 , 35 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. The BENEFIT trial prospectively demonstrated the feasibility of using liquid biopsy to guide the efficacy of first-line EGFR-TKI therapy for the first time.…”

A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer

“…However, tumor tissues for molecular profiling are not always available from advanced patients. Therefore, the use of tumor-derived cell-free DNA (cfDNA) isolated from body fluids, including plasma, pleural effusion (PE), cerebrospinal fluids, saliva, and urine, for cancer genomic profiling is being investigated (3)(4)(5)(6). Plasma derived cfDNA was widely accepted as a noninvasive option for tumor genomic profiling in patients with advanced stage malignancies, and also gained popularity for detecting tumor evolution and monitoring minimal residual disease in the era of precision medicine.…”