Impact of detecting plasma EGFR mutations with ultrasensitive liquid biopsy in outcomes of NSCLC patients treated with first- or second-generation EGFR-TKIs

2021 ◽  
pp. 1-13
Author(s):  
Oscar Arrieta ◽  
Juan-Manuel Hernández-Martínez ◽  
Edgar Montes-Servín ◽  
David Heredia ◽  
Andrés F. Cardona ◽  
...  
Keyword(s):  
Disease Progression ◽  
Clinical Characteristics ◽  
Detection Rate ◽  
Second Generation ◽  
Elevated Serum ◽  
Positive Finding ◽  
Response Evaluation ◽  
Mutational Status ◽  
Nsclc Patients ◽  
Egfr Tkis

BACKGROUND: Few trials have evaluated the utility of liquid biopsies to detect epidermal growth factor receptor mutations (EGFRm) at the time of response evaluation and its association with the clinical characteristics and outcomes of non-small-cell lung cancer (NSCLC) patients. OBJECTIVE: This study aimed to evaluate, in a real-world clinical setting, the prevalence of plasma EGFRm and its association with the clinical characteristics, response and survival outcomes of NSCLC patients under treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This observational study enrolled advanced or metastatic NSCLC patients, with confirmed tumor EGFRm, receiving treatment with first- or second-generation EGFR-TKIs. Blood samples for the detection of plasma EGFRm were collected at the time of response evaluation and processed using the Target Selector™ assay. The main outcomes were the detection rate of plasma EGFRm, median Progression-Free Survival (PFS) and Overall Survival (OS) according to plasma EGFR mutational status. RESULTS: Of 84 patients, 50 (59.5%) had an EGFRm detected in plasma. After a median follow-up of 21.1 months, 63 patients (75%) had disease progression. The detection rate of plasma EGFRm was significantly higher in patients with disease progression than in patients with partial response or stable disease (68.3% versus 33.3%; P< 0.01). PFS and OS were significantly longer in patients without plasma EGFRm than among patients with plasma EGFRm (14.3 months [95% CI, 9.25–19.39] vs 11.0 months [95% CI, 8.61–13.46]; P= 0.034) and (67.8 months [95% CI, 39.80–95.94] vs 32.0 months [95% CI, 17.12–46.93]; P= 0.006), respectively. A positive finding in LB was associated with the presence of ⩾ 3 more metastatic sites (P= 0.028), elevated serum carcinoembryonic (CEA) at disease progression (P= 0.015), and an increase in CEA with respect to baseline levels (P= 0.038). CONCLUSIONS: In NSCLC patients receiving EGFR-TKIs, the detection of plasma EGFRm at the time of tumor response evaluation is associated with poor clinical outcomes.

scholarly journals Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0181867 ◽  
Author(s):  
Roxana Alina Tudor ◽  
Adrijana D'Silva ◽  
Alain Tremblay ◽  
Paul MacEachern ◽  
Don Morris ◽  
...  
Keyword(s):  
Disease Progression ◽  
Clinical Outcomes ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

Impact of the presence of EGFR mutation on definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: Pattern of relapses and survival analyses in 145 patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
Shigehiro Yagishita ◽  
Hidehito Horinouchi ◽  
Tomoko Taniyama ◽  
Shinji Nakamichi ◽  
Satoru Kitazono ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Egfr Mutations ◽  
Definitive Chemoradiotherapy ◽  
Mutational Status ◽  
First Relapse ◽  
Nsclc Patients ◽  
Egfr Tkis

7540 Background: EGFR mutational status is an important biomarker in advanced NSCLC patients. However, little is known about the frequency and clinical significance of the presence of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) eligible for definitive chemoradiotherapy (CRT). Methods: Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive NSCLC patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year relapse-free rate, first relapse sites, and overall survival were investigated according to the EGFR mutational status. Results: A total of 528 patients received CRT at the National Cancer Center Hospital during the study period. Of these, 274 were diagnosed as having non-squamous NSCLC, and sufficient specimens for mutational analyses could be obtained from 145 patients. EGFR mutants (EGFR-mt) were found at a frequency of 18% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/ light smoker), the proportion of cases with smaller (T1/2) primary lesions was higher in patients with EGFR-mt than in those carrying wild-type EGFR (EGFR-wt). EGFR-mt showed a slightly better RR (85.7% vs. 72.9%), but similar median PFS (12.2 m vs. 10.6 m) and 2-year relapse free rates (23.8% vs. 29.2%) as compared to EGFR-wt. Local recurrence as first relapse occurred less frequently in EGFR-mt than in EGFR-wt (6% vs. 20%). After disease progression, a majority of EGFR-mt received EGFR-TKIs (62%), and these patients showed longer post-progression survival and a higher 5 year survival rate (60% vs. 40%) than EGFR-wt. Conclusions: Among the LA-NSCLC patients eligible for definitive CRT analyzed, 18% had EGFR- activating mutations. Although definitive CRT was similarly effective in both EGFR-mt and EGFR-wt, slightly better local control rate was noted in EGFR-mt. Treatment with EGFR-TKIs contributed to longer post-progression survival and overall survival in LA-NSCLC patients harboring EGFR mutations.

scholarly journals Tetracyclines increase the survival of NSCLC patients treated with EGFR TKIs: a retrospective nationwide registry study

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000864
Author(s):  
Virve Alanen ◽  
Sanna Iivanainen ◽  
Martti Arffman ◽  
Jussi Pekka Koivunen
Keyword(s):  
Second Generation ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Epidermal Growth ◽  
Prophylactic Use ◽  
Nsclc Patients ◽  
First And Second Generation ◽  
Egfr Tki ◽  
Egfr Tkis

BackgroundWith the first and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with tetracyclines, but it is unknown whether the use of tetracyclines can increase the survival of non-small-cell lung cancer (NSCLC) patients treated with EGFR TKIs.MethodsWe collected all the patients (n=1271) who had reimbursement for EGFR TKIs (gefitinib, erlotinib and afatinib) in Finland 2011–2016, had purchased TKIs, and had data available at nationwide cancer registry. The survival was analysed from the first EGFR TKI purchase to death or end-of follow-up, and patients were stratified according to TKIs, purchases of antibiotics, their ATC class and timing.Results802 (63.1%) patients had antibiotic purchases −14 to +200 days from the first EGFR TKI purchase, 447 of these tetracyclines. 322 (25.3%) had had purchased antibiotics −14 to +14 days (prophylaxis) from the first EGFR TKI purchase, 188 of these tetracyclines. Purchase of antibiotics was associated with improved survival (HR 0.80, 95% CI 0.71 to 0.91), which limited to tetracycline purchases only (HR 0.72, 95% CI 0.64 to 0.82). The largest survival benefit was seen with the prophylactic use of tetracyclines (HR 0.74, 95% CI 0.62 to 0.88). The benefit from tetracyclines was limited to erlotinib only (HR 0.68, 95% CI 0.58 to 0.78) which was retained in multivariate analysis. Prophylactic use of tetracyclines was associated with a longer erlotinib treatment duration (HR 0.81, 95% CI 0.61 to 0.96) but not with dose reductions or treatment breaks.ConclusionsTetracyclines improve the survival of NSCLC patients treated with the first and second-generation EGFR TKIs and they should be considered as a prophylaxis when initiating EGFR TKIs with high incidence of rash.

scholarly journals The Role of De Novo T790M Mutation in The Origin of T790M Resistance Clone and in The Clinical Outcomes For Advanced EGFR-Mutant NSCLC Patients Receiving EGFR-TKIs

2021 ◽  
Author(s):  
Mei-Fang Li ◽  
Jing-Hui Lin ◽  
Jing Zhang ◽  
Yun-Jian Huang ◽  
Sheng-Chi Chen ◽  
...  
Keyword(s):  
Disease Progression ◽  
De Novo ◽  
Resistance Mutation ◽  
Low Frequency ◽  
Third Generation ◽  
Resistance Mutations ◽  
T790m Mutation ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Abstract Background: Increasing evidence suggests that de novo T790M mutation occurs at a low frequency in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, the effects of this mutation on the formation of T790M resistant clones and efficacy of EGFR tyrosine kinase inhibitors (TKIs) remain unclear. Methods: Fifty-nine treatment-naïve in-patients with advanced EGFR-mutant NSCLC were enrolled in this study between 2017 and 2018. We dynamically monitored T790M mutation in ctDNA of patients before and during treatment with first-generation EGFR-TKIs, which were administered every 2 to 3 months until disease progression. Results: Among the patients, 28.81% (17/59) had a low-frequency de novo T790M mutation, 66.67% (10/15) of them retained T790M mutation and resistance in this group was defined as “selection” resistance. T790M mutation was detected after treatment in 42.3% (11/26) of patients without de novo T790M mutation who experienced disease progression and resistance in this group was defined as “acquisition” resistance. After treatment with third-generation EGFR-TKI, patients with the “selection” T790M resistance mutation had significantly better objective response rate (ORR) and longer progression-free survival (PFS) than those with the “acquisition” T790M resistance mutation. Conclusion: Our study provides evidence that low-frequency de novo T790M mutation is not rare in patients with advanced EGFR-mutant NSCLC. T790M resistance mutations can have two origins: the selection of low-frequency de novo T790M clones or the acquisition of the mutation in initially T790M-negative cells clinically. Since the origin of T790M resistance mutations can affect the efficacy of third-generation EGFR-TKIs, these EGFR-TKIs may be more effective for the treatment of NSCLC patients with “selection” T790M resistance mutations.

SHP2 Inhibition Benefits Epidermal Growth Factor Receptor mutated Non-Small Cell Lung Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Leiming Xia ◽  
Lu Wen ◽  
Siying Wang
Keyword(s):  
Stem Cells ◽  
Synergistic Effects ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Combination Strategies ◽  
Lung Cancer Therapy ◽  
Src Homology ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

: EGFR-TKIs are facing a big challenge of everlasting activated EGFR mutations which lack of effective binding sites, this barrier confers the dark sides that largely limited the outcome of NSCLC patients in clinic. Combination strategies show impressive anti-tumor efficacy comparing with EGFR-TKI mono-treatment, especially targeting both stem cells and non-stem cells. SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) plays an important role in regulating various malignant biology through hyper-activating intracellular pathways due to either over expression or catalytical mutation. Some pathways that SHP2 involved in were overlaps with EGFR downstream, and others were not subject to EGFR. Interestingly, SHP2 suppression was reported that can destroy the stemness of cancer. Therefore, we hypothesize SHP2 inhibitor might be an promising drug that could synergistically enhance or sensitize the anti-tumor efficacy of EGFR-TKIs in EGFR mutated NSCLC patients. Here, we summarized the mechanisms of SHP2 in regulating EGFR mutated NSCLC patients, attempted to reveal the potential synergistic effects of SHP2 inhibitor combined with EGFR-TKIs.

scholarly journals P76.47 Molecular Characteristics and Response to Diverse EGFR TKIs of NSCLC Patients Harboring EGFR E709-T710delinsX

2021 ◽  
Vol 16 (3) ◽  
pp. S607-S608
Author(s):  
W. Fang ◽  
C. Xu ◽  
X. Li ◽  
L. Zeng ◽  
X. Wang ◽  
...  
Keyword(s):  
Molecular Characteristics ◽  
Nsclc Patients ◽  
Egfr Tkis
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