Clinical performance of a comprehensive novel liquid biopsy test for identifying non-small cell lung cancer (NSCLC) patients for treatment with osimertinib.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9553-9553
Author(s):  
Jhanelle Elaine Gray ◽  
Ji-Youn Han ◽  
Aino Telaranta-Keerie ◽  
Xiangning Huang ◽  
Alexander Kohlmann ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Liquid Biopsy ◽  
Clinical Performance ◽  
Cox Model ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Single Nucleotide Variants ◽  
Biomarker Testing ◽  
Nsclc Patients ◽  
Egfr Tki

9553 Background: Genotyping is required to identify cancer patients (pts) eligible for targeted therapy; however, many do not receive biomarker testing, in part due to limitations associated with tissue-only genotyping practices and the growing list of biomarkers recommended to be tested. Liquid biopsy overcomes many of these limitations but is not yet fully adopted. We report here the clinical performance of a comprehensive liquid biopsy test based on next generation sequencing (NGS) of circulating tumor DNA (ctDNA) for the identification of NSCLC patients with EGFR exon 19 deletions (ex19del) or L858R mutations ( EGFRm) or EGFR T790M, eligible for treatment with osimertinib. Methods: 441 (79%) of 556 pts randomized in FLAURA (NCT02296125; first-line osimertinib vs comparator EGFR TKI in EGFRm NSCLC) and 300 (72%) of 419 pts from AURA3 (NCT012151981; osimertinib vs chemotherapy in NSCLC pts with T790M at progression on EGFR TKI) were retrospectively tested with Guardant360 (G360), a 74-gene ctDNA NGS assay assessing single nucleotide variants, insertion-deletions, amplifications, and fusions in genes relevant to targeted therapy selection as well as microsatellite instability. Progression-free survival (PFS) of pts with EGFRm or T790M detected by G360 was compared to pts detected by the cobas EGFR Mutation Test (cobas) using tissue or plasma with an unadjusted cox model. Results: Treatment with osimertinib was associated with a significant PFS benefit relative to control therapy in NSCLC pts with EGFRm (FLAURA) and T790M (AURA3) detected using G360 (Table). Observed clinical benefit for pts with EGFRm or T790M detected by G360 was similar to that for pts with EGFRm or T790M identified by cobas using tissue or plasma specimens. Conclusions: This analysis demonstrates that G360 accurately identifies pts for osimertinib therapy while simultaneously providing comprehensive genotyping for other therapeutic molecular targets. The application of NGS liquid biopsy has the potential to increase rates of pts genotyped and access to precision medicine. [Table: see text]

Circulating tumor DNA profiling to reveal heterogeneity of EGFR-TKI resistance mechanisms in lung adenocarcinoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11527-11527
Author(s):  
Rongrong Chen ◽  
Jun Zhao ◽  
Xingsheng Hu ◽  
Pingping Dai ◽  
Yuting Yi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Single Nucleotide Variants ◽  
Molecular Abnormalities ◽  
Activating Mutation ◽  
Tki Resistance ◽  
Egfr Tki ◽  
Tumor Dna

11527 Background: EGFR-TKI therapy has significantly improved prognosis of NSCLC patients with EGFR sensitive mutation. However, almost all patients ultimately develop PD while receiving TKI treatment. Circulating tumor DNA (ctDNA) is promising as a minimally-invasive liquid biopsy for comprehensive analysis of molecular abnormalities. Methods: A total of 254 advanced lung adenocarcinoma patients with signs of EGFR-TKI resistance were enrolled in the study. ctDNA was analyzed using next-generation sequencing based ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations across 59 genes. Results: ctDNA profiling was possible for all patients, 172 patients had ≥ 1 ctDNA alteration(s). Median number of plasma somatic mutations was 2, predominantly located in EGFR and TP53, with MET, ERBB2 and PIK3CA followed. Of that, 30.6% of mutations detected in ctDNA were at a frequency below 1%. In exploring the mechanisms of TKI-resistance, we found TKI-sensitizing mutations were not detected in plasma of 138 patients (54.3%). Known mechanisms such as EGFR T790M/C797S mutation, activating mutations of PI3K- AKT- mTOR signaling, amplification of MET, activating mutation / amplification of ERBB2, activating mutation of KRAS, BRAF or mutations in EGFR EX20 other than T790M/C797S were identified in 59, 16, 8, 7, 3, 2, and 2 patients respectively. T790M/C797S was detected in 50.8% of patients with plasma positive for TKI-sensitizing mutations. Of note, C797S was only detected in patients treated with AZD9291. EGFR amplification were identified in 15 patients, though whether it would result in TKI-resistance was still controversial. Co-occurrence of resistance mechanisms were observed in 22 patients including 13 patients without TKI-sensitizing mutations. Conclusions: There was a high frequency of inter and intra-patient heterogeneity of resistance mechanisms after EGFR TKI therapy. ctDNA can be used as a ‘liquid biopsy’ to facilitate the broad exploration of potential resistance mechanisms.

scholarly journals Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma

2020 ◽  
Vol 21 (23) ◽  
pp. 9083
Author(s):  
Catherine Taylor ◽  
Simi Chacko ◽  
Michelle Davey ◽  
Jacynthe Lacroix ◽  
Alexander MacPherson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Nsclc Patient ◽  
Egfr Mutations ◽  
Single Nucleotide Variants ◽  
Cell Free Dna ◽  
Free Dna ◽  
Nsclc Patients ◽  
Peptide Affinity

Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA. In this study, we evaluated whether peptide-affinity (PA) precipitation of EVs and cf-DNA from NSCLC patient plasma improves the sensitivity of single nucleotide variants (SNVs) detection and compared observed SNVs with those reported in the matched tissue biopsy. NSCLC patient plasma was subjected to either PA precipitation or cell-free methods and total nucleic acid (TNA) was extracted; SNVs were then detected by next-generation sequencing (NGS). PA led to increased recovery of DNA as well as an improvement in NGS sequencing parameters when compared to cf-TNA. Reduced concordance with tissue was observed in PA-TNA (62%) compared to cf-TNA (81%), mainly due to identification of SNVs in PA-TNA that were not observed in tissue. EGFR mutations were detected in PA-TNA with 83% sensitivity and 100% specificity. In conclusion, PA-TNA may improve the detection limits of low-abundance alleles using NGS.

scholarly journals Liquid biopsy in NSCLC: a new challenge in radiation therapy

2021 ◽  
Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Minimum Residual ◽  
Nsclc Patients ◽  
Choice Of Therapy ◽  
Tumor Dna

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.

A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14006-e14006
Author(s):  
Xiaotong Duan ◽  
Xiaoxia Zhu ◽  
Lijuan Wang
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Progression Free Survival ◽  
Driver Gene ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Nsclc Patients

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

EGFR-TKI benefit for NSCLC patients with EML4-ALK rearrangement.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18035-e18035
Author(s):  
Zhijie Wang ◽  
Jie Wang ◽  
Yi Long Wu ◽  
Hua Bai ◽  
Xu-Chao Zhang ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Mutant Type ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tki

e18035 Background: EML4-ALK rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). To identify the biological profiles of these patients, we examined the clinico-pathologic characteristics and treatment outcomes of NSCLC patients based on EML4-ALK and EGFR mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization (FISH) confirmed by immunohistochemistry (IHC), and EGFR mutations were determined using denaturing high-performance liquid chromatography (DHPLC). Results: Of the 151 patients screened, 113 had complete follow-up data as an analysis set. The incidence of EML4-ALK was 9.7% (11/113) using FISH, in which 10 cases had sufficient specimens for IHC confirmation and all were positive. Overall, EML4-ALK and EGFR mutations were largely mutually exclusive (p = 0.033), although two patients harbored concurrent mutations. EML4-ALK rearrangement was associated with resistance to EGFR-TKIs compared with the EGFR mutant type and WT/Nonrearrangement type (p = 0.001 for objective response rate; p = 0.004 for disease control rate; p = 0.021 for progression-free survival [PFS]). In terms of patients who received platinum-based doublet chemotherapy, no significant differences were observed in PFS between the EML4-ALK type, EGFR mutant type, and WT/Nonrearrangement type. Moreover, two patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared with single EML4-ALK-rearranged patients. Conclusions: This study presents several biological features of EML4-ALK NSCLC. It is largely mutually exclusive to EGFR mutations, resistant to EGFR-TKI. Coexistence of ALK rearrangement and EGFR mutation in patients with advanced NSCLC might represent a separate genotype with unique biological characteristics.

A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19166-e19166 ◽  
Author(s):  
Guanghui Gao ◽  
Shengxiang Ren ◽  
Aiwu Li ◽  
Yayi He ◽  
Xiaoxia Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Overall Response ◽  
Nsclc Patients ◽  
Egfr Tki

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% confidence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity profiles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.

Monitoring of circulating tumor DNA in non-small cell lung cancer patients treated with EGFR-inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11535-11535
Author(s):  
Remy B Verheijen ◽  
Tirsa T van Duijl ◽  
Michel M van den Heuvel ◽  
Jos H. Beijnen ◽  
Jan H.M. Schellens ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Free Survival ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Over Time

11535 Background: Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are routinely used in the treatment of non-small cell lung cancer (NSCLC). Monitoring of EGFR mutations in circulating tumor DNA (ctDNA) derived from plasma has been proposed as an alternative for repeated tumor biopsies. Our aim was to investigate the dynamics of ctDNA in a cohort of NSCLC patients and explore the roles of EGFR driver and resistance mutations in predicting disease progression and progression free survival (PFS). Methods: NSCLC patients treated with either erlotinib or gefitinib as first-line anti-EGFR therapy were included. Clinical data was collected retrospectively from medical records. Plasma samples collected as part of routine care were analyzed. First DNA was isolated from plasma using the QIAsymphony SP (Qiagen). Then EGFR driver (L858R and exon 19 deletions) and resistance (T790M) mutations were quantified using the X100 Droplet Digital PCR and analyzed using QuantaSoft software (Bio-Rad). The dynamics of ctDNA mutations over time and the relationship between copy numbers and progression free survival were explored. Results: 68 NSCLC patients and 249 plasma samples (1-13 per patient) were included in the analysis. In 33 patients, the T790M mutation was detected. The median (range) T790M concentration in these samples was of 7.3 (5.1 - 3688.7) copies/mL. In 30 patients, the L858R or exon 19 deletion driver mutations were found in median concentrations of 11.7 (5.1 – 12393.3) and 27.9 (5.9 – 2896.7) copies/mL, respectively. Using local polynomial regression, the copies/mL of EGFR driver mutations increased several weeks prior to progression on standard response evaluation. In Kaplan-Meier analysis, patients with a detectable T790M mutation during the first 8 weeks of treatment had a shorter PFS (7.6 versus 14.4 months, p < 0.01, log-rank test). Conclusions: Early detection of the T790M mutation in plasma ctDNA is related to poor PFS. Furthermore, an increase in the copies/mL of the EGFR driver mutation over time may predict clinical progression.

NGS to reveal heterogeneity between cerebrospinal fluid and plasma ctDNA among non-small cell lung cancer patients with leptomeningeal carcinomatosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9022-9022 ◽  
Author(s):  
Ben-Yuan Jiang ◽  
Yangsi LI ◽  
Shaokun Chuai ◽  
Zhou Zhang ◽  
Jin-Ji Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Leptomeningeal Carcinomatosis ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

9022 Background: In current clinical setting, NSCLC patients harboring specific driver mutation were usually treated guiding by prior profiling of the primary tumor when developed to brain metastasis. Some studies have shown that circulating tumor DNA (ctDNA) derived from cerebrospinal fluid (CSF) can reveal unique genomic alterations present in brain malignancies. We assessed CSF as a liquid biopsy media and compared to matched plasma. Methods: We performed capture-based ultra deep sequencing on ctDNA derived from matched CSF, plasma of 40 non-small cell lung cancer (NSCLC) patients with suspected leptomeningeal carcinomatosis (LC) using a panel consisting of 168 genes. Results: Among the 40 suspected LC cases, 35 were confirmed to have LC, ctDNA in CSF from the 5 non-LC cases are all undetectable. Circulating tumor DNA was detected in 93.8% of CSF and 66.7% of plasma. We compared mutation profiles and identified 86 and 46 SNVs from CSF and plasma, respectively, with 42 SNVs overlapping. Furthermore, ctDNA from CSF revealed many copy number variations (CNVs) that were not detected from plasma (189 CNVs vs. 3 CNVs). The average maximum allelic fraction (AF) of CSF ctDNA is significantly higher than in plasma (56.7% vs. 4.4% p < 10^-6). Twenty-eight patients were pre-treated with EGFR-TKIs and developed subsequent resistance. EGFR T790M and MET amplification were detected in 21% and 39% in CSF, respectively, showing a unique resistance profile among leptomeningeal metastases patients compared to the general population. Interestingly, 60% of CSF samples harbor TP53 loss of heterozygosity, only 11% of which were detected in the matched plasma samples. Such heterogeneity may reflect unique biological themes for brain metastatic tumor sub-clones. Furthermore, 26 patients received molecular targeted therapy based on the results from CSF, and 23 reported alleviation of symptoms at subsequent evaluations. Conclusions: Collectively, our data reveal that ctDNA derived from CSF provides a unique and more comprehensive characterization of genomic alterations of leptomeningeal carcinomatosis than plasma, supporting the importance of CSF as a liquid biopsy media.

ctDNA detection of EGFR mutations in NSCLC patients using TargetSelector.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23037-e23037
Author(s):  
Frans Beerkens ◽  
Chul Kim ◽  
Syed P. Hasan ◽  
Deepa Suresh Subramaniam ◽  
Stephen V. Liu ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Egfr Mutation ◽  
Stage Iv ◽  
Detection Sensitivity ◽  
Egfr Mutations ◽  
Blood Draw ◽  
Mutation Status ◽  
Activating Egfr Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

e23037 Background: EGFR mutations are the most frequent targetable genomic alterations in non-small cell lung cancer (NSCLC) patients (pts). While tissue biopsy remains the standard for assessing of EGFR mutation status, it is invasive and not always feasible. Liquid biopsy is a minimally invasive alternative. Biocept’s proprietary TargetSelector system evaluates circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood. We aimed to clinically validate the accuracy of EGFR-specific TargetSelector in NSCLC pts. Methods: At three time points (T0: baseline before TKI, T1: during EGFR-TKI therapy, T2: after progression), blood samples were collected in Biocept OncoCEE BCT validated to preserve DNA up to 8 days. These samples were interrogated for three EGFR mutations: exon 19 deletions (Del 19), L858R, and T790M. The objectives are to assess detection sensitivity of liquid biopsy using EGFR mutation status vs the tissue as gold standard and to evaluate whether the detection sensitivity changes with EGFR-TKI therapy. Results: A total of 53 study pts were enrolled (male, 21; female, 32). The mean age was 70.6 (range: 46 – 90). Most pts had stage IV disease (43, 81.1%) and lung adenocarcinoma (48, 90.6%). 26 (49.1%) pts had EGFR mutations in tumor tissue: Del 19, 13; L858R, 8; T790M, 6; other, 8. Detection sensitivity for sensitizing EGFR mutations (Del 19 and L858R) at T0, T1, and T2 was 60.0% (6/10), 33.3% (5/15), and 33.3% (1/3), respectively. There was no statistical difference in CTC counts between activating EGFR mutation-positive and -negative pts (mean CTC count: 10.5 vs 20.1; p = 0.11 by two-sided t-test). Detection sensitivity for T790M was 33.3% (2/6) and 5 of 6 pts were receiving T790M directed therapy (3, rociletinib; 2, osimertinib) at the time of blood draw. Two pts – one patient before initiation of EGFR-TKI and the other during treatment with erlotinib – were found to have T790M mutations only in blood and not in tissue. Conclusions: Activating EGFR mutation detection may decrease during the course of TKI therapy, possibly due to treatment response. Further research with an expanded sample size and serial collections are needed to evaluate this finding, and to investigate possible implications of the presence of T790M only in blood.

Molecular characteristics of EGFR exon 20 uncommon R776H mutation and response to osimertinib in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21001-e21001
Author(s):  
Gaili An ◽  
Li He ◽  
Xifang Wang ◽  
Yu Lei ◽  
Dejian Gu ◽  
...  
Keyword(s):  
First Generation ◽  
Cell Clone ◽  
Progression Free Survival ◽  
Molecular Characteristics ◽  
Treatment Naïve ◽  
Tki Treatment ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Ngs Data ◽  
Egfr Tki

e21001 Background: EGFR R776H is an uncommon exon 20 mutation in non-small cell lung cancer (NSCLC) patients. This mutation was first reported in samples after first generation EGFR TKI treatment as an acquired resistant mutation to first generation of EGFR-TKI. We further analyzed the molecular characteristics of patients with EGFR R776H mutation and its correlation with EGFR TKI therapy. Methods: In this study, a total of 16131 NSCLC patients from multiple centers with NGS data were retrospectively analyzed to study the molecular characteristics and clinical outcomes of patients with EGFR R776H mutation. Results: 44 of the 16131 patients (0.27%) had EGFR R776H mutation, and 28 of them (63.6%) were treatment-naïve while performing the mutation test. TP53 was the most common concomitant mutation in both treatment-naïve (57.1%) and treated (81.3%) patients. EGFR R776H mutation was found to coexist with multiple types EGFR mutation. The common mutations were EGFR L858R (54%) and EGFR G719A/S (25%), but It almost never coexists with 19del (2%). The coexist of EGFR R776H mutation was similar in both treatment-naïve and treated patients. In 16 of treated patients, all had received first - or second-generation EGFR TKI treatment, and the median progression-free survival (PFS) was 9 months. Interestingly, four of them found the presence of not only EGFR R776H but also EGFR T790M. It may be that EGFR R776H and T790M appear together in drug resistance, or it may be that EGFR R776H and EGFR sensitive mutation are not in the same cell clone. Two patients with EGFR R776H received treatment of Osimertinib and achieved partial response. The PFS of two patients in Osimertinib were 11 and 10 months, respectively. Moreover, EGFR C797S mutation was detected in two patients after resistant to Osimertinib. Conclusions: Presence of EGFR R776H mutation was rare in NSCLC patients and our retrospective study provides clinical evidence that Osimertinib could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients with EGFR R776H.

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