TKI Followed by Thoracic Radiotherapy for Stage IV EGFR Mutant NSCLC

2019 ◽  
Author(s):  
Keyword(s):  
Stage Iv ◽  
Thoracic Radiotherapy ◽  
Egfr Mutant

Upfront thoracic radiotherapy to primary lession improve outcomes in patients with stage IV non-small cell lung cancer harboring EGFR mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21167-e21167
Author(s):  
Ayse Kotek Sedef ◽  
Ahmet Taner Sümbül ◽  
Berna Akkus Yildrim ◽  
Erkan Topkan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Egfr Mutations ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Primary Tumor Site ◽  
Egfr Mutant

e21167 Background: The role of thoracic radiotherapy in the treatment of metastatic EGFR mutant non-small cell lung cancer patients in literature datas are insufficient.The aim of this study was to examine the effectiveness of upfront thoracic radiotherapy in metastatic EGFR mutant NSCLC patients treated with chemotherapy or TKI. Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 141 patients with metastatic EGFR mutant non-small cell lung cancer who has followed in two different oncology centers at Turkey between 2014 and 2020. have been included to this study. Results: The median age of the patients was 63 (range 35-91) years. EGFR mutation results of exon 19 deletion, exon 21 mutation and exon 18 mutation were found in 82 (58.2%), 56 (39.7%) and 3 (2.1%) patients, respectively. The median follow-up time was 22 months and 94 (33.3%) patients died during follow-up. Median overall survival (OS) was 26 months and progression free survival (for first line treatment) (PFS) was 10 months for whole patients, respectively. Radiotherapy was given to the primary tumor site in 32 (22,6%) patients. Patients receiving radiotherapy to primary tumor site had better overall survival than those not (31 versus 23 months respectively and p = 0,02) The survival advantage was also seen for patients group taking TKI at upfront setting (33 versus 23 months respectively and p = 0.05). Conclusions: In this study, we have showed that upfront thoracic radiotherapy to primary lession as combination with EGFR-TKI treatment may improve the outcome in advanced stage IV NSCLC patients harboring EGFR mutations.

Phase I dose-escalation study of thoracic radiotherapy in combination with gefitinib in patients with IIIB/IV non-small cell lung cancer (NCT00497250)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14581-e14581
Author(s):  
M. Fan ◽  
L. Xie ◽  
X. Xu ◽  
G. Zhang ◽  
J. Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Chemotherapy Regimen ◽  
Locally Advanced ◽  
Stage Iv ◽  
Stage Iiib ◽  
Thoracic Radiotherapy ◽  
Dose Escalation Study ◽  
Failure Patterns ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

e14581 Background: Cinical studies have confirmed that gefitinib, an EGFR-TKI, is effective for some advanced NSCLC patients. Patients with Asian ethnicity are reported to have a higher response rate with gefitinib monotherapy. However, a higher incidence of interstitial lung disease, sometimes lethal, is also found. The combination of gefitinib and radiotherapy has been observed to have a synergistic, anti-proliferative effect against NSCLC in vitro. This phase I study assessed the safety, clinical feasibility and optimally tolerated regimen (OTR) of this combination in patients with pretreated locally advanced or metastatic (IIIB/IV) NSCLC. Methods: Patients with stage IIIB or selected stage IV, failure of platinum-based chemotherapy regimen NSCLC were eligible. Four Cohorts of eight patients each were planned to be treated with escalating doses from 54 to 60 Gy of conformal or intensity- modulated radiotherapy (2Gy/Fx) administered in combination with gefitinib 250mg daily during RT and 60 days after the completion of RT to determine the OTR. Results: Since June 2007, 2 cohorts, a total of 16 patients, were enrolled and treated: 8 stage IIIB and 8 stage IV; 2 squamous-cell carcinoma and 14 adenocarcinoma; 8 smokers and 8 nonsmokers. Prior-chemotherapy regimen was consisted of NP, GP and TP for a median of 3.5 cycles (range, 1–5). Median follow-up time was seven months. Mean progression-free survival time was 5.2 months (median, 3.9; range, 1.7–12.3). Overall, adverse events were mild to moderate in severity. The most frequent grade 2 events included pneumonitis (31%) and dysphagia (19%). There were one treatment-related grade 3 event, which was nausea, and no grade 4 events. Most of the failure patterns were out-of-field (11/13) and the most common distant metastasis organ was the lungs. Three patients are progression-free to date. Conclusions: Thoracic radiotherapy up to 56 Gy concurrent with gefitinib 250 mg daily was well tolerated and clinically active in this group of pretreated Chinese NSCLC patients, including nonsmokers with adenocarcinoma. Accrual is continuing. Sponsorship: This work was partly supported by Program for New Century Excellent Talents in University (NCET), Ministry of Education. No significant financial relationships to disclose.

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.

scholarly journals Detailed Analysis and Radiomic Prediction of First Progression Sites of First-Line Targeted Therapy for EGFR-Mutant Lung Adenocarcinoma Patients With Systemic Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyang Li ◽  
Runping Hou ◽  
Wen Yu ◽  
Xueru Zhu ◽  
Hongwei Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Stage Iv ◽  
Clinical Information ◽  
Ct Images ◽  
First Line ◽  
Systemic Metastasis ◽  
Pre Treatment ◽  
Tki Treatment ◽  
Egfr Mutant

BackgroundWe aimed to analyze the first progression sites of first-line tyrosine kinase inhibitor (TKI) treatment for EGFR-mutant lung adenocarcinoma patients with systemic metastasis to recognize the potential candidates who might benefit from radiotherapy and establish a radiomic-based model to predict the first progression sites.Materials and MethodsWe retrospectively collected the clinical information and pre-treatment chest CT images of patients in Shanghai Chest Hospital from 2013 to 2017. All patients were diagnosed with stage IV EGFR-mutant lung adenocarcinoma and received TKI as first-line treatment. The first progression sites and survival were analyzed. The pre-treatment chest non-contrast CT images were utilized to establish a radiomic-based model to predict the first progression sites.ResultsWe totally collected 233 patients with systemic metastasis, among whom, there were 84 (36.1%) and 149 (63.9%) patients developing first progression in original lesions (OP) and new lesions (NP), respectively. The PFS and OS of patients with OP were longer than those with NP (PFS 11 months vs. 8 months, p = 0.03, OS 50 months vs. 35 months, p = 0.046). For 67.9% of the patients with OF, disease progressed within five sites (oligoprogression). The radiomic-based model could predict the progression sites with an AUC value of 0.736, a specificity of 0.60, and a sensitivity of 0.750 in the independent validation set.ConclusionAmong patients with systemic metastasis, there were 36.1% of patients developing OP at first progression who had a better prognosis than those developing NP. Patients with OP may be potential candidates who might benefit from radiotherapy. Radiomics is a useful method to distinguish patients developing OP and could provide some indications for radiotherapy.

scholarly journals MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression

2016 ◽  
Vol 34 (7) ◽  
pp. 721-730 ◽  
Author(s):  
Mark M. Awad ◽  
Geoffrey R. Oxnard ◽  
David M. Jackman ◽  
Daniel O. Savukoski ◽  
Dimity Hall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Subtype ◽  
Stage Iv ◽  
Small Cell ◽  
Chromosome 7 ◽  
Small Cell Lung ◽  
Genomic Amplification ◽  
Lung Cancers ◽  
Never Smokers ◽  
Egfr Mutant

Purpose Non–small-cell lung cancers (NSCLCs) harboring mutations in MET exon 14 and its flanking introns may respond to c-Met inhibitors. We sought to describe the clinical, pathologic, and genomic characteristics of patients with cancer with MET exon 14 mutations. Patients and Methods We interrogated next-generation sequencing results from 6,376 cancers to identify those harboring MET exon 14 mutations. Clinical characteristics of MET exon 14 mutated NSCLCs were compared with those of NSCLCs with activating mutations in KRAS and EGFR. Co-occurring genomic mutations and copy number alterations were identified. c-Met immunohistochemistry and real-time polymerase chain reaction to detect exon 14 skipping were performed where sufficient tissue was available. Results MET exon 14 mutations were identified in 28 of 933 nonsquamous NSCLCs (3.0%) and were not seen in other cancer types in this study. Patients with MET exon 14–mutated NSCLC were significantly older (median age, 72.5 years) than patients with EGFR-mutant (median age, 61 years; P < .001) or KRAS-mutant NSCLC (median age, 65 years; P < .001). Among patients with MET exon 14 mutations, 68% were women, and 36% were never-smokers. Stage IV MET exon 14–mutated NSCLCs were significantly more likely to have concurrent MET genomic amplification (mean ratio of MET to chromosome 7, 4.3) and strong c-Met immunohistochemical expression (mean H score, 253) than stage IA to IIIB MET exon 14–mutated NSCLCs (mean ratio of MET to chromosome 7, 1.4; P = .007; mean H score, 155; P = .002) and stage IV MET exon 14–wild-type NSCLCs (mean ratio of MET to chromosome 7, 1.2; P < .001; mean H score, 142; P < .001). A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib. Conclusion MET exon 14 mutations represent a clinically unique molecular subtype of NSCLC. Prospective clinical trials with c-Met inhibitors will be necessary to validate MET exon 14 mutations as an important therapeutic target in NSCLC.

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