KRAS and EGFR status as predictive markers of response and time to progression in EGFR wild-type stage IV non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine-kinase inhibitors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19000-e19000
Author(s):  
Manuel Domine ◽  
Federico Rojo ◽  
Tatiana Hernandez ◽  
Sandra Zazo ◽  
Gloria Serrano ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Copy Number ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Wild Type ◽  
Time To Progression ◽  
Egfr Amplification ◽  
Combined Analysis ◽  
Nsclc Patients ◽  
Egfr Tki

e19000 Background: KRAS mutations on codons 12, 13 and 61 result in the constitutive activation of protein, which may render tumor cells independent of epidermal growth factor receptor (EGFR) signalling and thereby resistant to tyrosine-kinase inhibitor (TKI) therapy in NSCLC patients. This study was aimed to evaluate the associations of KRAS and EGFR copy number alteration and mutations with response and time to progression (TTP) in EGFR TKI-treated patients. Methods: 84 samples from NSCLS patients treated with erlotinib or gefitinib were analyzed for KRAS and EGFR mutation status by cobas KRAS and EGFR Mutation Tests (Roche). EGFR copy number was determined by fluorescent in situ hybridization (FISH, Abbott Molecular) and amplification was defined with three or more gene copies in tumor. Results: KRAS mutation was detected in 15 (17.8%) cases, EGFR mutation in 27 (32.1%) and EGFR amplification in 8 (9.5%). Significant differences were detected in response rates for wild-type (0.2) and mutant KRAS (0.0) (p=0.023), for wild-type (0.12) and mutant EGFR (0.39) (p=0.007), and for non-amplified (0.18) and EGFR-amplified (0.71) patients (p=0.005). Additionally, significant benefit from TKI therapy was observed for KRAS wild-type compared with KRAS-mutated patients (median TTP 7 vs. 3 months, p=0.001), for EGFR-mutated compared with wild-type patients (14 vs. 4 months, p=0.004) and for EGFR-amplification in contrast to non-amplified cases (11 vs. 5 months, p=0.001). KRAS and EGFR mutations or EGFR amplification did not correlated with overall survival (18 vs. 19 months, p=0.406; 16 vs. 21 p=0.094; 25 vs. 17 months, p=0.103, respectively). Combined analysis of favourable status of three biomarkers strongly predicted benefit to TKI therapy (median TTP 15 vs. 3 months, p<0.001). Conclusions: Combined analysis ofKRAS mutation, EGFR mutation and EGFR amplification in EGFR TKI-treated NSCLC might provide superior predictive information than single biomarker study in these patients.

Lungful: An observational prospective study to assess the molecular epidemiology of EGFR mutations upon progression on or after first line EGFR-TKI therapy, in real-life clinical settings in Greece.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21641-e21641
Author(s):  
Giannis Socrates Mountzios ◽  
Dimitrios Mavroudis ◽  
Epaminondas Samantas ◽  
Anna Koumarianou ◽  
Evangelos Georgios Konstantinos Fergadis ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Second Generation ◽  
Egfr Mutation ◽  
Locally Advanced ◽  
Real Life ◽  
Egfr Mutations ◽  
Liquid Biopsies ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

e21641 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the gold standard 1st line strategy for non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations (EGFRm), associated with improved survival outcomes and quality of life compared to chemotherapy. Despite the high response rate with first- and second- generation TKIs, most patients develop resistance to treatment and progress. The acquisition of T790M mutation in exon 20 is considered the most common resistance mechanism. This study aims to investigate the molecular epidemiology of EGFR resistance mutations, focusing on T790M in EGFRm NSCLC patients treated with TKIs. Methods: The study included patients with locally advanced/metastatic EGFRm NSCLC who have progressed on or after 1st line treatment with first- or second- generation TKI. Samples either from plasma-based liquid biopsy and/or tissue re-biopsy were analysed using the Cobas EGFR Mutation Test v2. All patients signed informed consent and were enrolled between July 2017 and September 2019. Statistical analyses were performed using SAS software, Version 9.4. Results: Ninety-six eligible patients were enrolled. At the time of progression, T790M mutation was detected in 16.7%of the patients using plasma-based liquid biopsies. Among patients with negative T790M result, in plasma, tissue re-biopsy was performed in 22,7% with evaluable/valid results in 72.2% of them. T790M mutation was identified in 38.5% of re-biopsy samples. According to Cobas EGFR Mutation test results (combined plasma and tissue), T790M mutation was identified in 21.9% of the patients. Of T790M-positive patients 42.9% had previously received first and 57.1% second generation EGFR-TKI. Conclusions: Results from this study in real world clinical setting in Greece, show that EGFR-T790M acquired resistance positivity rate in plasma is lower compared to previous reports. Moreover, these data underline the challenges of implementing precision medicine using tissue re-biopsy in advanced/metastatic NSCLC. Clinical trial information: D133FR00126. [Table: see text]

EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): Results of a prospective phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
V. A. Miller ◽  
M. Zakowski ◽  
G. J. Riely ◽  
W. Pao ◽  
M. Ladanyi ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Kras Mutation ◽  
Copy Number ◽  
Egfr Mutation ◽  
Phase Ii Trial ◽  
Time To Progression ◽  
Exon 2 ◽  
Egfr Amplification ◽  
Correlative Studies

7003 Background: Erlotinib produces dramatic responses in a subset of patients with NSCLC. Mutations in the EGFR tyrosine kinase domain, EGFR amplification or polysomy and EGFR overexpression on immunohistochemistry have all been associated with sensitivity and benefit; pts with KRAS mutation are commonly resistant to this agent. These correlative studies were prospectively undertaken to characterize the ability of these markers to predict response rate, time to progression and survival in pts with BAC treated with the EGFR-TKI, erlotinib. Methods: One hundred and two patients received erlotinib as part of a phase II trial in BAC (Kris, Proc ASCO 2005); 84 had one or more correlative studies completed. Analysis of EGFR exons 19 and 21 (n=82) (Pao, et al PNAS 2004), EGFR IHC (n=62) (DAKO) was performed and EGFR copy number was determined by chromogenic in situ hybridization (CISH) (n=74) (Zymed); detection of ≥ 4 signals per cell was considered evidence of amplified copy number. KRAS exon 2 (n=79) testing was performed by direct sequencing. Fisher’s exact test was used to study the association of each feature in pts with partial response or no partial response. Time to progression and survival were analyzed with log-rank test. Results: See table below. Conclusions: 1) EGFR exon 19 or 21 mutation is a powerful predictor of response and TTP but not OS in pts with BAC treated with erlotinib. 2) CISH ≥4 is associated with response and improved TTP but not OS. 3) Patients with both EGFR mutation and amplification fare well supporting the concept of “oncogene addiction”; erlotinib should be considered as initial therapy in this population. 4) EGFR amplification without mutation is uncommon. 5) There is no clear utility of EGFR IHC in clinical decision making. 6) The presence of KRAS mutation predicts resistance to erlotinib. Supported, in part, by Genentech. [Table: see text] [Table: see text]

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.

Exploring the applicability of immunotherapy in different EGFR mutation subgroups based on data analysis of 9,659 Chinese patients with NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21020-e21020
Author(s):  
Hao Peng ◽  
Hushan Zhang ◽  
Libin Zhang ◽  
Yang Wang ◽  
Xudong Shen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Egfr Mutation ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Tissue Samples ◽  
Nsclc Patients

e21020 Background: Here we assessed TMB level, PD-L1 expression, and their correlation in 9649 Chinese NSCLC patients with or without EGFR mutation, and different subtypes of EGFR mutations, to find out the underlying mechanisms that different outcomes of ICI for EGFR wild type and EGFR mutation NSCLC patients, and the possibility of ICI therapy for NSCLC patients of different EGFR mutation subtypes. Methods: Tumor tissue samples of 9649 NSCLC patients were collected from Janary 2018, expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Gene mutation was detected by means of next generation sequencing (NGS). Performed Whole-Exome Sequencing (WES) on 70 tissue samples and corresponding White Blood Cells (WBCs) as matched control. Other samples were detected with panel covering whole exon regions of 733 cancer related genes. All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: Results showed that the proportion of EGFR mutation in Chinese patients with NSCLC was 51.3%, and the proportion of EGFR mutation subtypes were 42.6% L858R, 39.5% exon 19del, 2.3% exon 20in, 4.3% T790M. These samples were divided into different groups according to EGFR mutation, both WES based and panel-based results showed that EGFR wild type group displayed higher TMB level than EGFR mutation group (P < 0.05). However, except for exon 19del, L858R, exon 20in, no significant differences were found between wild type and other EGFR mutation subtypes. Furthermore, results of IHC revealed that, higher proportion of strong positive PD-L1 expression (TPS≥50) were found in EGFR wild type than exon 19del, L858R and exon 20in, no significant correlation was found between TMB level and PD-L1 expression. Conclusions: EGFR mutations account for half of Chinese NSCLC patients. The biomarkers of immune checkpoint inhibitors (such as TMB and PD-L1) are different in various EGFR mutation subtypes, which may indicate that for some NSCLC patients with EGFR mutation subtypes, they may also respond to ICI treatment as wild-type.

Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7076-7076 ◽  
Author(s):  
A. Sutani ◽  
Y. Nagai ◽  
K. Udagawa ◽  
Y. Uchida ◽  
Y. Murayama ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Response Rate ◽  
Phase Ii Study ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Wild Type ◽  
First Line ◽  
Egfr Gene ◽  
Nsclc Patients ◽  
Egfr Genes

7076 Background: The responsiveness to gefitinib has been reported to closely link to the presence of EGFR gene mutations. We developed a method, PNA-LNA PCR clamp, capable of detecting EGFR mutations in the presence of 100-fold background of wild type EGFR from normal cells (Can Res. 2005;65:7276). This study was prospectively designed to evaluate 1) the sensitivity and the specificity of the PNA-LNA PCR clamp (sample size > 100 pts) and 2) a phase II study of gefitinib for NSCLC patients (pts) with EGFR gene mutations (sample size > 25 pts to show the lower limit of 95% CI > 50%). Methods: Clinical samples (sputum, pleural effusion, bronchial fluid and paraffin tissue) were obtained from consecutive NSCLC pts with informed consent in our institution, and were tested by the PNA-LNA PCR clamp. After the second informed consent, for PS 0–2, inoperable stage III and IV pts with EGFR mutations, gefitinib (250mg P.O. daily) was given as the second treatment after docetaxel containing chemotherapy. In case of poor PS pts, the first line chemotherapy was omitted. Results: From Sept. ’04 to Oct. ’05, samples from 100 of a total of 107 pts were informative of EGFR mutation status. PNA-LNA PCR clamp detected EGFR mutations in 38 pts (38%) (15 males/23 females; median age:62; adenoca.:33 pts). Exon 19 deletions, L858R and L861Q were found in 25 (66%), 12 (32%) and 1 (2%) patients, respectively. But 62 pts (51 males/11 females; median age:66; Ad:43 pts) were judged to have wild type EGFR. Between positive and negative pts in EGFR mutation, there was significant difference in the distinction of sex (p = 0.00001). Gefitinib was given to 26 pts with EGFR mutations as the first line (4 pts) or the second line treatment (22 pts). One patient and 20 patients showed CR and PRs, respectively, and the response rate was 81% (95% CI: 61–94%). For patients with wild EGFR genes, gefitinib was given to 5 patients and one patient (20%) showed PR. The response rate was significantly different between wild and mutant EGFR genes detected by the PNA-LNA PCR clamp (p = 0.017). Conclusions: PNA-LNA PCR clamp could reliably detect EGFR mutations, indicating the method is useful to detect EGFR mutations in clinical specimens. Updated data will be presented at the meeting. No significant financial relationships to disclose.

Impact of EGFR mutation status on clinical outcome of nintedanib plus docetaxel in patients with previously treated non-small cell lung cancer (NSCLC): Retrospective analysis of Korean nintedanib named-patient usage (NPU) program in NSCLC (KCSG LU14-2).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20638-e20638
Author(s):  
Sook-hee Hong ◽  
Ho Jung An ◽  
Yun-Gyoo Lee ◽  
Hoon-Kyo Kim ◽  
Seung-Sei Lee ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Egfr Mutations ◽  
Clinical Activity ◽  
Good Tolerability ◽  
Mutation Status ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Tki

e20638 Background: Anti-angiogenic agents have been reported to have clinical activity for NSCLC harboring EGFR mutation (mutEGFR) with/without EGFR Tyrosine kinase inhibitor (TKI). We report clinical outcomes of nintedanib plus docetaxel for refractory NSCLC patients conducted by virtue of Korean NPU program. Methods: Patients with NSCLC were eligible if they failed at least one prior systemic treatment. Docetaxel was administered with 75 or 60mg/m2 on D1 or 37.5mg/m2 on D1, D8 every 3 weeks plus nintedanib 200mg orally twice daily. Nintedanib treatment was continued until disease progression or unacceptable toxicity after 4-6 cycles of combination therapy. Results: Of 62 patients enrolled, 23 patients had activating EGFR mutations (14 in exon19 deletion, 7 exon21 L858R/L861Q, 1 exon20 duplication, and 1 in both exon19 deletion and exon20 T790M) and progressed during prior EGFR-TKI treatment. Of 23 patients, 22 had progressed during or after platinum doublet chemotherapy. Only for 2 patients, EGFR mutation status was unknown. The majority of patients were heavily pretreated, with 43.7% received nintedanib plus docetaxel as ≥ 4th line therapy. 4 patients had prior bevacizumab treatment. Objective response rate (ORR) was 22.9%. Median PFS and OS were 3.9 months (95% CI 3.1-4.6) and 9.5 months (95% CI 5.3-13.7), respectively. Depending on EGFR mutation status, ORR in mutEGFR group was higher than wtEGFR group (30.4% vs 20%, p= 0.50) and median PFS in mutEGFR group was significantly longer than wtEGFR group (6.1 vs 3.3 months, p= 0.008). No treatment related death was reported. Common grade 3/4 adverse events were neutropenia (58.3%) and reversible elevated liver enzyme (18.8%). Conclusions: Taken together, nintedanib plus docetaxel showed meaningful clinical activity with good tolerability for refractory NSCLC patients. Our data suggest that this combination may be a recommendable regimen for EGFR-TKI-resistant mutEGFR NSCLC.

scholarly journals Outcomes of 27 Non-Small Cell Lung Cancer Patients Receiving Resections of Paired Primary Pulmonary and Brain Metastatic Tumours: Is EGFR Negative Mutation of Brain Metastasis Bring More Benefit?

2021 ◽  
Author(s):  
Shuonan Xu ◽  
Jianfei Zhu ◽  
Daixing Zhong ◽  
Yanmin Xia ◽  
Yingsheng Wen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Lung Tumour ◽  
Wild Type ◽  
Small Cell Lung ◽  
Mutant Type ◽  
Paired Tumour ◽  
Nsclc Patients ◽  
Primary Lung Tumour

Abstract Background: To analyze the heterogeneity and clinical outcomes of epidermal growth factor receptor (EGFR) gene mutation in primary tumour and corresponding brain metastasis(BM) in non-small cell lung cancer (NSCLC).Methods: Primary pulmonary tumours and paired metastatic brain tumours were surgically removed from twenty-seven NSCLC patients from July 1999 to November 2013 in our hospital. All brain lesions were confirmed as metastases stemming from NSCLC by pathological examination. EGFR gene (exons 18-21) mutant status was detected in matched tumour by using amplification refraction mutation system (ARMS). If inconsistency was detected, the paired tumour was evaluated again. The McNemar test was performed to compare the consistency of the paired tumour, and the Kappa test was used to quantify the agreement of both methods.Progression free survival(PFS) and overall survival(OS) were exhibited by the Kaplan-Meier.Results: In this study, of the 27 patients, nine (33.3%) cases were found to have EGFR mutations in BMs, and ten (37.0%) patients were detected positive EGFR status in primary lung tumour tissue. The rate of consistency of the matched tumour was 24/27 (88.9%, P≤0.001), and the Kappa coefficient was 0.757. Among the three cases presenting EGFR mutational heterogeneity, two patients harbored EGFR mutation in primary tumors but was negative in BMs, meanwhile, the other patient had the opposite pattern. Comparing to patients with consistent EGFR mutations(both mutant or wild),patients with inconsistent EGFR mutations tended to have better outcomes, including PFS(37.2months vs 25.0months vs 16.5months,P=0.159) and OS(53.6months vs 27.5months vs 26.8months,P=0.380), further analysis showed that two patients whose EGFR mutant-type primary tumor progressing to wild-type cerebral metastastic tumor might have longer overall survival(53.6months,37.8months) than one patient harboring reverse mutant difference(EGFR wild-type primary tumor progressing to mutant-type brain metastastic tumor) (16.7months). Also we found that patients with wild type in brain metastatic tumour had longer overall survival (OS)(mOS, 36.3 months vs 29.1months, P = 0.944).Conclusions: EGFR mutation status in NSCLC patients between primary lung tumour and paired BM was heterogeneous, patients harbored wild type EGFR mutation in BM might have better outcomes, especially for positive status transferred to wild.

A novel mutant-enriched liquidchip for detection of circulating EGFR mutations in advanced non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14526-e14526
Author(s):  
S. Lu ◽  
H. Yang ◽  
X. Ye ◽  
X. Xu ◽  
Z. Li ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Nsclc Patients ◽  
Exon 19

e14526 Background: We developed a novel technology, Mutant-enriched liquidchip (MEL), which integrates the sensitive mutant enriched PCR and quantitative high throughput liquidchip (suspension array), to detect circulating EGFR mutations (Exon 19 deletion and exon 21 L858R mutation) in patients with advanced non-small cell lung cancer (NSCLC). Methods: To enrich mutant EGFR, a unique restriction site is introduced into the mutation alleles so that the wild type sequence can be selectively removed by restriction digestion, and the undigested mutated DNA is amplified by PCR. The product is then hybridized to complementary probes (including 15 types of exon 19 deletion and exon 21 L858R mutation) which had been conjugated to beads coding with different fluorescent dye, followed by measuring through Luminex 200 system. Plasmid DNA mixture with different EGFR genotypes was applied to determine the sensitivity and accuracy of MEL. Afterwards, the MEL was validated in 49 patients whose EGFR genotypes of tissue specimen had been tested with direct sequencing The circulating genomic DNA was obtained from serum sample of other 201 Chinese stage IIIB or IV NSCLC patients without EGFR-TKI administration, and the EGFR mutation status was analyzed by using of MEL. Results: The results shows that MEL is capable of detecting as few as 20 copies of mutant EGFR alleles with a sensitivity limit of at least mutant/wild-type ratio of 0.1%. It also shows that MEL can not only confirm EGFR mutations status in tissue specimens already known by direct sequencing (13/49), but also detect mutations in some of those showing wild type by sequencing (16/49). Overall, 54% of patients had circulating EGFR mutation. 34% of patients had an exon 19 deletion and 29.6% had L858R. 63.1% of mutations were found in females and 67.6% in never-smokers. Conclusions: This novel MEL method allows for highly sensitive and reproducible detection of human somatic mutations in heterogeneous specimens, and could be applicable to test EGFR mutations non-invasively in advanced NSCLC patients for predicting response to targeted therapy. No significant financial relationships to disclose.

Cytokeratin 19 fragment (CYFRA21-1) to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) harboring EGFR mutation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10610-10610
Author(s):  
Kosuke Tanaka ◽  
Akito Hata ◽  
Reiko Kaji ◽  
Shiro Fujita ◽  
Jumpei Takeshita ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Egfr Mutation ◽  
Predictive Marker ◽  
Egfr Mutations ◽  
Significant Difference ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

10610 Background: EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR mutated patients treated with EGFR-TKIs. Methods: We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results: Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA21-1 level (>2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with normal CYFRA21-1 level (median PFS 7.5 vs 14.0 months, p=0.006). No significant difference in PFS was observed between high CEA group (>5 ng/ml) and normal CEA group (median PFS 8.6 vs 11.2 months, p=0.2423). Multivariate analysis revealed that high CYFRA21-1 level is independently associated with PFS (HR 1.35; p=0.002) as well as squamous cell carcinoma (HR 1.40; p=0.020) and performance status 2-4 (HR 2.63; p=0.003). No statistically significant difference in overall survival (OS) was observed between high CYFRA21-1 group and normal group (median OS 24.8 vs 39.1 months, p=0.104). Conclusions: High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. Serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR mutated patients can be divided into two subgroups according to CYFRA21-1 level at initial diagnosis.

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