Utility of nonsurgical diagnostic specimens in cellular differentiation and molecular profiling (EGFR mutation and EML4-ALK detection) of NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18061-e18061
Author(s):  
Victor Cohen ◽  
Amanda Levitt ◽  
Goulnar Kasymjanova ◽  
Jason Scott Agulnik ◽  
Amr Al Banna ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Body Fluid ◽  
Cellular Differentiation ◽  
Egfr Mutation ◽  
Mutational Analysis ◽  
Accurate Determination ◽  
Primary Objective ◽  
Egfr Mutations ◽  
Histologic Diagnosis ◽  
Mutation Status

e18061 Background: The utility of different non-surgical specimens for the accurate determination of cellular and molecular attributes in NSCLC has yet to be established. The primary objective of this study was to determine and compare the yield of non-surgical specimens for the accurate cellular differentiation of NSCLC and analysis of EGFR and EML4-ALK mutations. Methods: Patients with a histologic diagnosis of NSCLC from January 2004 to September 2010 were included. Diagnosis was based on cytological characteristics and IHC analysis. Fragment analysis and real-time PCR methods were used for EGFR mutation detection. EML4-ALK rearrangements were detected by FISH. Diagnostic specimens were divided into pathology specimens (PS) and cytology specimens (CS). PS included surgical and non-surgical biopsies. CS included FNA (TBNA and TTNA) and body fluid samples. These groups were compared using χ2 analyses. Yield of histologic analysis was compared in a subgroup of patients who underwent both surgical and non-surgical procedures. Results: 715 patients were included in the study. The yield of CS when compared to PS was lower for cellular differentiation (76% vs. 91%, p <0.0001) and IHC (70% vs. 89%, p <0.0001). Among the CS, TTNA provided better yield than TBNA for cellular differentiation (89% vs. 67%, p < 0.0001) and IHC (85% vs. 72%, p = 0.023). 94 patients underwent both surgical and non-surgical procedures. As compared to surgical biopsies, the yield of non-surgical procedures for cellular classification was 81% in body fluid samples, 68% in FNA, and 88% in non-surgical biopsies. 320 patients were tested for both EGFR and EML4-ALK mutations. The yield of CS versus PS was lower for EGFR mutation status (74% vs. 93% p < 0.0001). Among the CS, TTNA provided better yield than TBNA for EGFR mutation analysis (90% vs. 70%, p = 0.045) and body fluid samples were least likely (59%) to provide EGFR mutation status. Three EML4-ALK FISH-positive cases were identified. All samples were PS. All EML4-ALK positive cases tested negative for EGFR mutations. Conclusions: Non-surgical lung biopsy specimens can yield sufficient samples for histologic assignment and mutational analysis.

CONCORDANCE study: An observational, multicenter, prospective study to evaluate concordance of detecting EGFR mutations by circulating tumor-free DNA versus tissues biopsy in NSCLC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21615-e21615
Author(s):  
Kumar Prabhash ◽  
Bivas Biswas ◽  
Sachin Khurana ◽  
Ullas Batra ◽  
Ghanashyam Biswas ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Real World ◽  
Egfr Mutation ◽  
Tissue Sample ◽  
Primary Objective ◽  
Egfr Mutations ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Free Dna ◽  
Sample Testing

e21615 Background: Epidermal growth factor receptor (EGFR) mutations on circulating tumour free DNA (ctDNA) by liquid biopsy is suitable option in those with difficulty in obtaining tissue samples. Correlation in tissue and plasma results of EFGRm has not been established in the Indian population. 1,2,3 This study was done to investigate the utility of ctDNA for EGFRm testing with Next-Generation Sequencing (NGS) in a real-world diagnostic setting. Methods: This is a multicentre, prospective, diagnostic observational study in 245 newly diagnosed treatment naïve, histologically confirmed, advanced lung adenocarcinoma patients. This was a single visit study. The primary objective of the study was to determine the level of concordance between EGFR mutation status obtained by tissue and ctDNA from blood (plasma) based testing in terms of overall concordance, sensitivity & specificity. Study was registered at Clinicaltrials.gov NCT03562819 & CTRI/2018/08/015290. Results: Seventy-five (30.6%) and eighty-four (34.3%) subjects showed positive mutation status by plasma & tissue testing respectively. The overall concordance of 82.9% was observed between tissue and ctDNA (Plasma) based testing. Sensitivity of EGFR mutation status between ctDNA and tissue was observed for EGFR mutation subtypes was observed to be 100% while specificity was observed to be 90.1%. Plasma and tissue sample testing detected 1.2% (n = 3) and 2.4% (n = 6) positive in exon 20 T790M EGFR mutation, respectively. In terms of secondary outcomes, plasma sample testing detected 16.7% (n = 41) positive for Exon 19 deletions type EGFR mutation followed Exon 21 L858R [11.4% (n = 28)]. Conclusions: CONCORDANCE, a real-world study in Indian patients suggest that ctDNA testing for EGFR mutation analysis is a diagnostic option in newly diagnosed lung adenocarcinoma patients. EGFR Mutation testing in ctDNA, being non-invasive and especially in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies. [Table: see text]

scholarly journals Tissue or blood: which is more suitable for detection of EGFR mutations in non-small cell lung cancer?

2018 ◽  
Vol 33 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Rong Biaoxue ◽  
Yang Shuanying
Keyword(s):  
Lung Cancer ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Operating Characteristic Curve

Background: Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference. We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. Methods: Investigations that provided data on EGFR mutation status in blood were searched in the databases of Medline, Embase, Ovid Technologies and Web of Science. The detect efficiency of EGFR mutations in paired blood and tissues was compared using a random-effects model of meta-analysis. Pooled sensitivity and specificity and diagnostic accuracy were calculated by receiver operating characteristic curve. Results: A total of 19 studies with 2,922 individuals were involved in this meta-analysis. The pooled results showed the positive detection rate of EGFR mutations in lung cancer tissues was remarkably higher than that of paired blood samples (odds ratio [OR] = 1.47, p<0.001). The pooled sensitivity and specificity of blood were 0.65 and 0.91, respectively, and the area under the receiver operating characteristic curve was 0.89. Conclusions: Although blood had a better specificity for detecting EGFR mutations, the absence of blood positivity should not necessarily be construed as confirmed negativity. Patients with negative results for blood should decidedly undergo further biopsies to ascertain EGFR mutations.

Immunohistochemistry Profile Predicts EGFR Mutation Status in Lung Adenocarcinoma

2020 ◽  
Vol 28 (5) ◽  
pp. 502-506
Author(s):  
Wencheng Li ◽  
Angela G. Niehaus ◽  
Stacey S. O’Neill
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Mutation Status ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Napsin A ◽  
Therapeutic Decisions

Significant advances in targeted therapy have been made in recent years for patients with lung adenocarcinoma. These targeted therapies have made molecular testing of paramount importance to drive therapeutic decisions. Material for testing is often limited, particularly in cytology specimens and small core biopsies. A reliable screening tool is invaluable in triaging limited tissue and selection for epidermal growth factor receptor ( EGFR) mutation testing. We hypothesized that the immunohistochemistry (IHC) profile of lung adenocarcinoma predicts EGFR mutation status. In this retrospective study, we evaluated the thyroid transcription factor-1 (TTF-1)/napsin A IHC profile and EGFR mutation status in 339 lung adenocarcinomas at our academic institution. In our cohort, we found that 92.3% of cases were positive for TTF-1 and/or napsin A by IHC with an EGFR positivity rate of 17.3%. Importantly, 7.7% of the cases were dual TTF-1/napsin A negative, and none of these cases contained EGFR mutations. This finding supports the use of TTF-1 and napsin A IHC to identify cases where EGFR mutation status will be negative, thus preserving limited tissue for other ancillary testing.

scholarly journals Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 803 ◽  
Author(s):  
Ming-Szu Hung ◽  
Jr-Hau Lung ◽  
Yu-Ching Lin ◽  
Yu-Hung Fang ◽  
Shu-Yi Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Circulating Tumor Dna ◽  
Egfr Mutations ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
First Line ◽  
Mutation Status ◽  
Egfr Tki ◽  
Tumor Dna

Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77–0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0–11.8, vs. 15.0 months, 95% CI 11.7–28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4–37.2, vs. 55.6 months, 95% CI 25.8–61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis.

scholarly journals Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival

2014 ◽  
Vol 48 (2) ◽  
pp. 173-183 ◽  
Author(s):  
Karmen Stanic ◽  
Matjaz Zwitter ◽  
Nina Turnsek Hitij ◽  
Izidor Kern ◽  
Aleksander Sadikov ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Lung Adenocarcinoma ◽  
Cumulative Incidence ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Course Of Disease ◽  
Epidermal Growth ◽  
Egfr Mutant

AbstractBackground. The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7670-7670
Author(s):  
K. Hotta ◽  
K. Kiura ◽  
S. Toyooka ◽  
N. Takigawa ◽  
J. Soh ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Egfr Mutation ◽  
Direct Sequencing ◽  
Receptor Gene ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Egfr Mutations ◽  
Second Line ◽  
First Line ◽  
Mutation Status

7670 Background: The relationship between EGFR mutation status and clinical outcome has not fully been assessed in NSCLC patients receiving cytotoxic agents. The aim of this study was to clarify its association. We also examined if this association could be affected by the prior gefitinib treatment or not. Methods: Patients with advanced or postoperative recurrent NSCLC who received both cytotoxic chemotherapy and gefitinib monotherapy through their treatment course and whose tumors were assessable for EGFR mutation analysis were included in this study. EGFR mutation was determined in exons 19 and 21 by direct sequencing. Results: Sixty patients were included in the study, including 6 (10%) patients who received the first-line gefitinib monotherapy followed by cytotoxic chemotherapy in the second-line or later settings. Of the 54 (90%) patients, 22 also underwent subsequent cytotoxic chemotherapy after the relapse to gefitinib monotherapy. EGFR mutations were detected in 17 (28%) patients. In the first-line cytotoxic chemotherapy setting (n=54), EGFR mutations significantly affected progression-free survival (PFS) with 6-month PFS rates of 45.8 vs. 21.9% (p=0.05). This was also observed in the multivariate analysis (HR=0.42, p=0.04). EGFR mutation was also significantly correlated with overall survival (OS) in the multivariate analysis (HR=0.26, p <0.01). Contrary, in the 28 (47%) of 60 patients who received cytotoxic chemotherapy after gefitinib monotherapy, there were no differences in PFS stratified by EGFR mutation status. The sensitivity to gefitinib was, however, correlated with EGFR mutation status and its sensitivity was retained even in the second-line setting in patients with EGFR mutations. Conclusion: EGFR mutation was significantly associated with better PFS in the first-line cytotoxic chemotherapy regimens. However, its association was not observed in the cytotoxic regimens administered after the relapse to gefitinib monotherapy, while the sensitivity to gefitinib was associated with EGFR mutation even in the second-line or later setting. No significant financial relationships to disclose.

A comparison of bronchofiberscopic (BFS) washing cytology (BWC) and formalin-fixed paraffin-embedded tissue (PPFE) in the analysis of EGFR mutations in advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8054-8054
Author(s):  
Naoya Hida ◽  
Yuuki Misumi ◽  
Yoko Agemi ◽  
Akira Sato ◽  
Mari Ishii ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
High Reliability ◽  
High Sensitivity ◽  
Mutation Testing ◽  
Egfr Mutations ◽  
Mutation Site ◽  
Mutation Status ◽  
Bronchial Washing ◽  
Egfr Mutation Testing

8054 Background: In the treatment of advanced NSCLC, EGFR mutation status is one of the most predictive factors for the efficacy of EGFR tyrosine kinase inhibitors, and the evaluation of EGFR mutation status using the PPFE has been widely used for this analysis throughout the world. However, whether BWC can be used as an alternative for PPFE in the analysis of EGFR mutations is unknown. The largest study evaluating these 2 methods included only around 20 samples. Therefore, in the current study, we compared the freeze stock solution of BWC with PPFE for the determination of EGFR mutation status in a large sample set. Methods: In diagnostic BFS examinations, after curetting or brushing and biopsy to target lesions, subsequent bronchial washing by saline was performed. Thereafter, the saline fluid in which the forceps were washed and the bronchial washing fluid were mixed in a sterilized tube and were immediately frozen in a -20°C freezer. EGFR mutation testing for both BWC and PPFE was performed using high-sensitivity PCR (BML, PCR-Invader). Results: A total of 440 BFS examinations were performed from Aug 2010 to Nov 2011 in our hospital. The BWCs of 268 suspected cases of lung cancer were successfully obtained. Of these, 51 cases that were pathologically confirmed as adenocarcinoma based on both BWC and PPFE were analyzed in this study. EGFR mutations were identified in 25 cases, while the remaining 26 cases had wild-type EGFR. In 49 of 51 cases, the results of EGFR mutation status were the same for BWC and PPFE, and the concordance rate was 96%. In one case, an exon-18 mutation was detected only by BWC. In another case an exon-21 mutation was detected only by PPFE. In 24 of 25 cases of EGFR mutation, the mutation site was the same in both samples. The kappa coefficient was 0.92. Conclusions: This is the largest genetic study to date demonstrating a head-to-head comparison of BWC and PPFE for the evaluation of EGFR mutations. Both methods showed high reliability and concordance using high-sensitivity PCR. BWC is considered a simple, rapid method and represents an effective alternative for PPFE in EGFR mutation testing.

Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20032-e20032
Author(s):  
Qin Feng
Keyword(s):  
Tumor Tissue ◽  
Egfr Mutation ◽  
Circulating Tumor Dna ◽  
Egfr Mutations ◽  
Amplification Refractory Mutation System ◽  
Circulating Dna ◽  
Mutation Status ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Egfr Tkis

e20032 Background: Tumor tissue is currently used for EGFR testing non-small cell lung cancer (NSCLC) patients, but the detection of circulating tumor DNA (ctDNA) is being actively investigated as a new method for the detection and longitudinal monitoring of actionable mutations in plasma samples. Around 30% patients with EGFR mutation presented inconsistent status of EGFR mutation between in tissues and plasma. We compared EGFR mutation detection in circulating tumor DNA from blood to that in matched tissue. Methods: EGFR mutation status were assessed by the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd.) both in tissue and plasma. Retrospective analysis to evaluate the concordance of tissue and plasma EGFR determination for assessing eligibility for EGFR-TKIs therapy in NSCLC patients. 10 mL tubes of blood were collected from patients who never had been treated by EGFR TKI, and plasma circulating tumor DNA were extracted from plasma by Biomark Circulating DNA Kit. Qubit2.0 Fluorometer was used to make plasma circulating DNA tumor quantitation. The concentration of final DNA sample is ≦2ng/μl. Results: A total of 224 NSCLC patients were detected by Amplification Refractory Mutation System (ARMS), with 92 tissue positive and 49 blood positive. Results showed 53.3% sensitivity in overall samples, but 81.4% sensitivity in ⅢB~Ⅲ patients. The specificity is 100%. Conclusions: The high sensitivity and specificity between tissue and plasma EGFR determination supports the blood-based EGFR mutation testing to determinate the eligibility of NSCLC patients for EGFR-TKIs treatment, especialy in ⅢB~Ⅲ NSCLC patients. Blood, in particular plasma, is a good screening substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the blood negativity should be confirmed with other sample, biopsy tissue, pleural effusion, etc..

scholarly journals A Predictive Model of EGFR Mutation Status in Patients with Lung Adenocarcinoma Based on PET/CT Metabolic Indexes and Clinicopathological Variables

2020 ◽  
Author(s):  
Yanlong Yang ◽  
Shuchen Shi ◽  
Qianzhun Huang ◽  
Wenzhao Zhong ◽  
Juntao Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Growth Pattern ◽  
Egfr Mutation ◽  
Clinicopathological Characteristics ◽  
Metabolic Parameters ◽  
Smoking History ◽  
Egfr Mutations ◽  
Wild Type ◽  
Mutation Status ◽  
Pet Ct

Abstract PurposeThe purpose of this study was to create a mathematical model based on the metabolic parameters of PET/CT with clinicopathological characteristics to predict the EGFR mutation status of patients with lung adenocarcinoma.MethodsThis study retrospectively enrolled patients with lung adenocarcinoma who underwent surgical treatment at two centres in China between January 2012 and December 2015. PET/CT metabolic parameters and Classical EGFR mutation status detection by molecular pathology were performed before and after surgery, and we analysed the associations of EGFR mutation status with patient sex, age, smoking history, maximum primary lesion diameter, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), TNM stage and histopathological subtype of lung adenocarcinoma.ResultsA total of 310 patients were included, comprising 161 with EGFR mutations (51.9%) and 149 with wild-type EGFR (48.1%). EGFR mutations were more common in females, non-smokers, and those with stage IV disease, a low SUVmax, and ≤35 mm nodules, whereas wild-type EGFR was more common in males, smokers, and those with a solid growth pattern. Multivariate analysis suggested that liver SUVratio, smoking history, tumour size, TNM stage, and solid growth pattern can predict EGFR mutation status, and these factors were used to construct a mathematical model.ConclusionThe prediction model constructed in this study based on clinicopathological characteristics and PET/CT parameters might offer a basis by which to predict Classical EGFR status and provide a certain reference value for guiding the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with lung adenocarcinoma.

Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8089-8089
Author(s):  
J. M. Amann ◽  
J. Lee ◽  
H. Roder ◽  
J. Brahmer ◽  
J. Schiller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Egf Receptor ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
First Line ◽  
Serum Samples ◽  
Kras Mutations ◽  
Mutation Status ◽  
Molecular Features

8089 Background: An improved understanding of molecular features of cancers and cancer patients associated with benefit from targeted therapies could allow the rational personalization of therapies to increase the probability of efficacy and decrease toxicity and cost. Multiple biomarkers have been proposed for predicting benefit after therapy with EGF receptor targeted therapies in first line colon and second line lung cancer therapy. Methods: In this study, we analyzed available tumor and serum samples from ECOG 3503, a single arm phase II study of erlotinib in first line lung cancer, for mutations in Kras and EGFR, as well as the previously described serum MALDI proteomic classifier (Veristrat). Out of 137 enrolled patients, there were 93 serum samples and 43 tumor samples available. Results: Molecular analysis of a subset of tumors from patients enrolled in ECOG 3503 shows that 10/43 (23%) contained Kras mutations and 3/43 (7%) harbored EGFR mutations. Classification of the 93 available sera for the pattern of proteins previously published as associated with survival after treatment with gefitinib identified 68/93 (73%) as predicted to be “good” and 25/93 (27%) predicted to have poor survival. Of the 6 responders with available serum, 5 were classified as MALDI good. Correlation with survival demonstrated a highly statistically significant correlation with MALDI status (p < 0.001), and a marginally significant association of EGFR mutation with survival (p = 0.05), but no correlation with ras mutation status. Median survival was 10.8 months in MALDI good patients and 3.9 in MALDI poor patients. MALDI status was independent of both ras and EGFR mutation status. Conclusions: Thus, in distinct contrast to colon cancer, ras gene mutations do not appear to be associated with survival after first line EGFR-targeted therapy in lung cancer. The previously defined MALDI predictor is potent and highly clinically significantly associated with survival after first line treatment with erlotinib, and is independent of mutations in ras and EGFR in this dataset. [Table: see text]

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