scholarly journals 1225P The progression-free survival of the first-line EGFR-TKI is a strong prognosticator of the second-line osimertinib in non-small cell lung cancer (NSCLC) patients with EGFR-T790M mutation: A real-world study

2021 ◽  
Vol 32 ◽  
pp. S972
Author(s):  
X. Tang ◽  
W-L. Qian ◽  
T. Pang ◽  
Y-L. Gong ◽  
Z-G. Yang
Keyword(s):  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
T790m Mutation ◽  
Free Survival ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr T790m

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.

Detect T790M in cell free tumor DNA of Chinese advanced non-small cell lung cancer adenocarcinoma patients by different platforms and evaluate clinical outcomes of T790M positive patients with osimertinib monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9104-TPS9104
Author(s):  
Zhiyong Liang ◽  
Ying Cheng ◽  
Yuan Chen ◽  
Weiping Liu ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Digital Pcr ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Tumor Dna ◽  
Egfr T790m

TPS9104 Background: EGFR T790M mutation occurs in approximately 50-60% of non-small cell lung cancer adenocarcinoma (NSCLC) patients with acquired EGFR-TKI resistance, based on tumor re-biopsies using an invasive clinical procedure. Recently, Cell free tumor DNA (ctDNA) has emerged as a specific and sensitive blood-based biomarker and studies have demonstrated ctDNA as a feasible and minimally invasive alternative to tissue biopsy. Data on different technology platforms used for EGFR T790M detection in blood in China is limited. We aim to compare the methods currently available in hospital practise, including cobas EGFR Mutation Test (Roche Molecular Systems), super-ARMS, digital PCR and NGS, to compare each platform and clinically validate each as companion diagnostic to osimertinib. Methods: This is an open-label, multi-center study in 250 locally advanced or metastatic NSCLC patients with documented EGFR sensitizing mutation and progression on previous EGFR-TKI. T790M mutation in plasma ctDNA will be tested by four methods: cobas, super-ARMS, digital PCR and NGS in order to evaluate the concordance, sensitivity and specificity of T790M testing in plasma between the cobas test and the other platforms. T790M positive patients by any of the four platforms will receive osimertinib treatment (administered orally as one 80 mg tablet once a day in ASTRIS study, NCT02474355) and the clinical outcomes (PFS, ORR, OS) will be followed. Patients will continue to receive osimertinib until disease progression (PD), as assessed by investigators. Digital PCR and NGS will be used to monitor the molecular evolution of T790M and C797S in plasma from NSCLC patients during osimertinib treatment. NGS will also be used to explore acquired resistance mechanisms before osimertinib treatment and after PD. 23 of planned 250 patients have been enrolled in the study as of January 2017. Clinical trial information: NCT02997501.

scholarly journals A Multicenter Retrospective Study on the Prognosis of Stage III Unresectable Mutant Non-Small Cell Lung Cancer With Tyrosine Kinase Inhibitors Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Ranpu Wu ◽  
Shaorong Yu ◽  
Jinjun Ye ◽  
Yimin Wang ◽  
Zhiting Zhao ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Small Cell ◽  
Stage Iii ◽  
Driver Gene ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Nsclc Patients

BackgroundFor unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy is nowadays the standard treatment. Patients with advanced NSCLC harboring driver-gene mutations benefit from Tyrosine Kinase Inhibitors (TKIs) Therapy. In a real-world setting, there is room for exploring the benefit of TKIs in stage III unresectable NSCLC patients with mutation.MethodsA total of 81 patients from the Jinling Hospital and the Jiangsu Cancer Hospital with stage III unresectable mutant NSCLC applied targeted therapy were enrolled in this retrospective study. Patients with first-line application of TKIs were followed up to gain the situation of surgery qualifications, progression-free survival and overall survival, so as to evaluate the survival prognosis, then whether patients benefit and what kind of patients benefit most from TKI monotherapy treatment or its combination are explored.ResultsThe median progression-free survival of involved 81 patients was 13.87 months (95% confidence interval (CI): 11.66–16.08), and the median survival was 41.47 months (95%CI: 20.11–62.83). The 5-year survival rates were 91.0, 80.3, 56.1, 45.5, and 32.5%, respectively. After first-line TKI therapy, seven patients (8.6%) were reevaluated as eligible for surgery and proceeded to surgery. Although no characteristics were found to be statistical prognostic, younger female non-smokers still tended to have a better prognosis with longer progression free survival and overall survival.ConclusionsTKIs are a viable option for mutant stage III unresectable NSCLC patients who have achieved good clinical benefit from TKI. Patients who cannot tolerate chemoradiotherapy, especially those with driver gene mutations, can choose targeted therapy for first-line treatment.

Long progression-free survival with first-line paclitaxel plus platinum is associated with improved response and progression-free survival with second-line docetaxel in advanced non-small-cell lung cancer

2014 ◽  
Vol 74 (4) ◽  
pp. 681-690 ◽  
Author(s):  
Eleazar Omar Macedo-Pérez ◽  
Vicente Morales-Oyarvide ◽  
Víctor Osvaldo Mendoza-García ◽  
Yuzmiren Dorantes-Gallareta ◽  
Diana Flores-Estrada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

scholarly journals Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tereza Vaclova ◽  
Ursula Grazini ◽  
Lewis Ward ◽  
Daniel O’Neill ◽  
Aleksandra Markovets ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr T790m

AbstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

scholarly journals A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Liu ◽  
Jingjing Qu ◽  
Jianfu Heng ◽  
Chunhua Zhou ◽  
Yi Xiong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Real World ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tki Resistance ◽  
Egfr Tki

BackgroundMET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing.MethodsOf the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.ResultsThe objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1).ConclusionOur study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy.

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