Erlotinib in EGFR TKI-progressed lung cancer: Retrospective real-world insights from a tertiary cancer center in South India

e19004 Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of <10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(<10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P<0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p<0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P<0.001) and DCR(P<0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (< 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC. No significant financial relationships to disclose.

Background: Epidermal growth factor receptor (EGFR) inhibition with tyrosine kinase inhibitors (TKIs) has proven successful in the management of patients with non small cell lung cancer (NSCLC). However, clinical benefit is predominantly limited to the subgroup of patients with an activating EGFR mutation (10%). Treating the remaining 90% of patients with wild type (wt) EGFR is an unmet clinical need. Aim: To evaluate the effect of an allosteric AKT inhibitor (AKTi 1/2) in combination with the EGFR inhibitor gefitinib on cell proliferation, apoptosis and signalling output in EGFR mutant/wt NSCLC cell lines. Methods: Four NSCLC cell lines were selected: NCI-H522 and NCI-H1651 (EGFR wt and K-RAS wt), PC9 and HCC827 (EGFR mutant). The 96hr sulphorhodamine assays was used to assess the effect of gefitinib and AKTi 1/2 on growth inhibition, and median effect analysis to calculate combination indices (CIs) to assess the effect of both drugs in combination. The expression of p-EGFR, p-AKT, p-S6, p-ERK and cleaved PARP were studied by Western blotting in the EGFR wt NCI-H522 and the EGFR mutant PC9 cell lines. Results: EGFR wt cell lines NCI-H522 and NCI-H1651 were relatively resistant to gefitinib (IC50 values of 7.0 ± 2.5 uM and 8.8 ± 0.9 uM, respectively) compared with the EGFR mutant cell lines PC9 and HCC827 (IC50 values of 0.07 ± 0.03 uM and 0.004 ± 0.0005 uM, respectively). The combination of gefitinib and AKTi 1/2 produced synergistic inhibition of growth in both EGFR wild type and mutant cell lines. Synergism was more marked in EGFR wt cell lines with CI values (ED50) of 0.53 ± 0.28 and 0.49 ± 0.17 for NCI-H522 and NCI-H1651 respectively, compared with 0.74 ± 0.11 and 0.76 ± 0.14 for the EGFR mutant cell lines PC9 and HCC827, respectively. Concomitant exposure of cells to gefitinib and AKTi 1/2 for 24 hrs caused incremental inhibition of p-AKT, p-S6 and p-ERK in both the EGFR wt (NCI-H522) and EGFR mutant (PC9) cell lines. Gefitinib alone resulted in partial inhibition of AKT phosphorylation in PC9 cells and up-regulation in NCI-H522 cells. Incremental induction of cleaved PARP, a marker of apoptosis, was seen in PC9 cells treated with the combination of gefitinib and AKTi 1/2. Conclusions: These results demonstrate synergistic growth inhibition of EGFR wt and mutant NSCLC cell lines by the combination of gefitinib with AKTi 1/2. Additional pre-clinical studies are investigating this further. Clinical studies of the combination doublet are warranted to expand the utility of EGFR TKI in EGFR wt NSCLC. Citation Format: Martina Puglisi, Parames Thavasu, Adam Stewart, Jaishree Bhosle, Sanjay Popat, Mary E R O'Brien, Udai Banerji. Evaluation of combination of an EGFR and AKT inhibitor in EGFR mutant and EGFR wild type non-small cell lung cancer cells lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2441. doi:10.1158/1538-7445.AM2013-2441

Commentary: Another win for immunotherapy

BackgroundNon-surgical cytological specimens are adequate not only for accurate histological subtyping but also for molecular profiling. A modified amplification refractory mutation system polymerase chain reaction (ARMS PCR), known as SuperARMS PCR, was improved by optimizing the primers designation, which provides a higher sensitivity and specificity approach for free plasma DNA detection. It is unclear whether SuperARMS PCR detects epidermal growth factor receptor (EGFR) mutations in cytology samples. The aim of this study was to compare the EGFR mutations detected by ARMS PCR and SuperARMS PCR in cytology samples derived from advanced non-small cell lung cancer (NSCLC) patients.MethodsFrom March 2016 to March 2018, a total of 234 cytological samples were obtained from primary or metastatic lesions of NSCLC, including 144 fine-needle aspirations (FNAs), 36 endobroncheal ultrasonography (EBUS) FNAs, 36 transbronchial needle aspirations (TBNAs) and 18 pleural effusion (PLEs). EGFR mutations were simultaneously detected using an ADx-ARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China) and an ADx-SuperARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China). Digital droplet PCR (ddPCR) and next-generation sequencing (NGS) were further used to verify the EGFR mutant inconsistent samples.ResultsAll of the 234 patients with advanced or recurrent NSCLC were diagnosed and assessed by two cytopathologists, and their EGFR mutation statuses were successfully detected by ARMS and SuperARMS. Importantly, the SuperARMS and ARMS methods showed a highly concordant result of 94.0% (220/234) (95%CI: 85.0, 95.0%). The positive rate of the SuperARMS was higher than the ARMS in the cytology samples for EGFR detection (46.2% vs. 40.2%). The specific EGFR mutation sites in 16 samples (6.8%) were not completely consistent between the SuperARMS and ARMS. A total of 14 patients showed EGFR mutations when detected by SuperARMS, but by ARMS there were EGFR wild-type. Two patients were detected as having one more EGFR mutation site by SuperARMS than by ARMS. ddPCR and NGS were used to further confirm the EGFR mutations in these inconsistent samples. Eight samples had the same mutation results as the SuperARMS, and 6 samples were not verified because the remaining DNA was insufficient. A total of 78 EGFR mutation patients received Tyrosine Kinase Inhibitor (TKI) treatment. The overall objective response rate (ORR) was 88.5% (69/78) for EGFR TKI treatment.ConclusionSuperARMS showed a high sensitivity and specificity for EGFR detection and thus, is expected to become a routine test in the clinic to be used as a widely available, easy-to-operate and sensitive method for EGFR mutation detection in liquid-based cytology samples.

Epidermal growth factor receptor (EGFR) mutation is the key predictor of EGFR tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC). We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations. A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system (ARMS). We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate (ORR), disease control rate (DCR) and progression free survival (PFS). Of all patients, EGFR mutation rate was 28.6% (60/210) by direct sequencing and 45.2% (95/210) by ARMS (P<0.001) respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR (48.0% vs. 80.9%, P=0.004) and shorter median PFS (7.4 vs. 10.5 months, P=0.009) as compared with that of EGFR mutation positive patients by both detection methods. Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.

14008 Background: Both epidermal growth factor receptor (EGFR) mutation and gene copy number of HER2, a member of EGFR family, are associated with gefitinib sensitivity. We carried out a correlative study to determine the relationships between EGFR mutations, EGFR or HER2 protein expressions, their activation status (pEGFR, pHER2) or insulin-like growth factor receptor 1 (IGFR-1) protein expressions and clinical outcomes after gefitinib treatment in advanced NSCLC. Method: Tumors from patients (pts) were evaluated for EGFR mutations by DNA sequence, and for protein expressions of EGFR, pEGFR, HER2, pHER2 and IGFR-1 by immuno-histochemistry. Time to progression (TTP) was calculated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with TTP were evaluated with Cox proportional hazard regression modeling. Correlation between EGFR mutation and response was evaluated by Fisher’s direct method. Relationship between each protein expression and response was tested by two-sided. Primary endpoint was to detect biomarkers to predict gefitinib sensitivity. Results: From Dec. 2003 to Dec. 2005, 103 consecutive pts were enrolled onto the study, and received gefitinib until disease progression. Median age was 68 years, female (58%), adenocarcinoma (83%), never smoker (55%) and no previous chemotherapy (49%). 98 pts were evaluable for efficacies, toxicities and gene analyses. Forty-one pts (42%) had EGFR mutations; 14 pts had deletional mutation in exon 19, 27 pts had missense mutation (L858R) in exon 21. EGFR mutations were significantly related to response (62 vs. 26%; P = 0.001), disease control rate (92 vs. 65%; P = 0.003) and TTP (median, 10.1 vs. 5.1months; hazard ratio = 0.64; P = 0.048). Both pEGFR (0, +1 vs. =+2; P = 0.002,) and pHER2 (0 vs. =+1; P = 0.001) expressions are significantly associated with incidence of EGFR mutation. Conclusions: EGFR mutation was a significant predictive biomarker of response to gefitinib. Phosphorylated EGFR protein expression is a potent replaceable biomarker for EGFR mutation. No significant financial relationships to disclose.

High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Abbreviation: ALK = anaplastic lymphoma kinase, EGFR = epidermal growth factor receptor, NSCLC = non-small cell lung cancer, TKI = tyrosine kinase inhibitor

Objective: Several systematic reviews for Therapeutic Effect of Kanglaite Injection Plus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Versus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Alone In Stage IIIB Advanced Lung Adenocarcinoma have recently emerged evidence. However, limited data are available regarding the activity of available EGFR TKIs against uncommon EGFR mutations. This meta-analysis evaluates the efficacy of Kanglaite Injection Plus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Versus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Alone In Stage IIIB Advanced Lung Adenocarcinoma. So therefore, Lung Adenocarcinoma related diseases have a profound economic impact on health care systems global wide, thus Kanglaite Injection combined with First-Line EGFR –TKIs have been shown to have beneficial effects than treatment with First-Line EGFR Tyrosine Kinase Inhibitors (TKIs) Alone. Methods: We electronically searched the literature of the China National Knowledge Infrastructure (Chinese language, English 2010-2019), Pub Med, Cochrane Central Register of Controlled Trails from database inception, CNKI, web of science Wang Fang, and manually searched Chinese-language oncology journals to identify randomized controlled trials (RCTs) of Kanglaite Injection Plus First Line EGFR-TKIs Versus First Line EGFR- TKIs Alone, regardless of their having been published or not, blinding, duration of treatment, or duration of follow-up. The quality of the included trials was assessed using the method recommended by The Cochrane Collaboration (CC). If heterogeneity existed among subgroups, then overall results (OS) were calculated based on a random-effects model; otherwise, a fixed effects model was used. Results: Electronic database searches yielded 1780 citations with NSCLC. Articles or Records Excluded by screening of the title/abstract level total 510, Records which are not Rcts 430, Study with no EGFR mutation analysis 590, Due to duplicated publication 180. Finally, we identified full text articles retrieved for detailled evaluation 70. The sample size of each trial had calculated by Rev Man 5.3. Pooled analyses performed using both fixed- and random-effects models revealed that compared with First Line of Egfr-Tkis alone, KLT injection plus First Line of Egfr-Tkis improved the response rate (relative risk [RR}, 1.34; 95% CI, 1.19-1.51 and RR, 1.35; 95% CI, 1.2 0-1.51, respectively). KLT injection plus First Line of Egfr-Tkis was associated with improvement in the symptoms of cough, dyspnea, chest pain, fatigue, and anorexia.

Increased epidermal growth factor receptor ( EGFR) gene copy number is strongly associated with EGFR mutations and adenocarcinoma in non-small cell lung cancers: A chromogenic in situ hybridization study of 182 patients

8096 Background: Epidermal growth factor receptor (EGFR) mutations, amplification, and K-ras mutations are known as predictive factor of the EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients (pts) with NSCLC. Prognostic influences of those biomarkers remain the matter to be discussed. Methods: Consecutive pts with advanced NSCLC who were examined EGFR genotype and received 1st line cytotoxic chemotherapy were enrolled. EGFR amplification and K-ras mutation were analyzed if sufficient tumor samples were available. Results: 87 pts were enrolled in this study. EGFR mutations or K-ras mutations were found in 26 of 87 (29.9%) or 2 of 65 (3.1%) pts, respectively. As to objective response rate (ORR), no significant differences were observed among pts with EGFR mutations, K-ras mutations, and pts without both mutations. Progression free survival (PFS) in 1st line cytotoxic chemotherapy was 8.4, 1.0, and 3.9 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. PFS was longer in pts with EGFR mutations compared with the pts without both mutations (p=0.0234). We also found the pts with K-ras mutations had shorter PFS compared with pts without both mutations (p=0.0203). Overall survival (OS) was 29.7, 2.3 and 13.4 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. Significant differences were found between pts with EGFR mutation and without both mutations (p=0.0001) and between pts without both mutations and with K-ras mutations (p=0.0001). Pts with EGFR amplification were found in 21 of 78 (26.9%). There were no differences between EGFR amplification positive and negative in terms of ORR, PFS and OS. 87 of 68 (78.2%) pts received EGFR-TKI therapy in the second line or later. As previously reported, both EGFR mutations and amplifications were good predictive marker of ORR, PFS and OS in pts treated with EGFR-TKI. Conclusions: EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker in first line cytotoxic chemotherapy. There is the possibility that EGFR and K-ras mutations have the prognostic impact in advanced NSCLC. [Table: see text]

INTRODUCTION: Epidermal growth factor receptor (EGFR) is frequently expressed in triple-negative breast cancer and is emerging as a new therapeutic target. However, the rate of EGFR gene copy number alteration and mutation has been reported to be quite variable and their prognostic significance is poorly defined in triple-negative breast cancer. METHOD: We examined EGFR protein expression, gene copy number alteration and mutation in 150 cases of tripe-negative breast cancer and correlated their findings with clinical outcome of the patients. EGFR protein expression was evaluated by immunohistochemistry using whole tissue sections and EGFR copy number alteration was assessed by dual-color fluorescence in situ hybridization using tissue microarrays. EGFR mutation analysis was performed by polymerase chain reaction of exon 18 to 21 of EGFR gene and direct sequencing of PCR products. RESULT: EGFR protein was expressed in 117 of 150 cases (78.0%). High EGFR gene copy number was found in 33.3% of the cases (amplification in 2.0% and high polysomy in 31.3%). Five EGFR mutations were detected in 4 of 150 cases (2.7%) with G719A in exon 18 (n=1), V786M in exon 20 (n=1) and L858R in exon 21 (n=3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, was correlated with EGFR protein over-expression. In survival analyses, high EGFR copy number gain was found to be a poor prognostic factor for relapse-free survival (p=0.046), especially for metastasis-free survival (p=0.016). CONCLUSION: EGFR mutation is found to be a rare event in triple-negative breast cancer. However, high EGFR copy number is relatively frequent and is associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR gene copy number is beneficial for the prediction of outcome in patients with triple-negative breast cancer and selection of the patients for anti-EGFR targeted therapy. Citation Format: Heae Surng Park, Min Hye Jang, Eun Joo Kim, Hyun Jeong Kim, Hee Jin Lee, So Yeon Park. High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2396. doi:10.1158/1538-7445.AM2013-2396

Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011. Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutations (P < .05). Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.

e20518 Background: Epidermal growth factor receptor (EGFR) mutation have been demonstrated to be both predictive and prognostic for patients with metastatic lung cancer. The administration of EGFR tyrosine kinase inhibitors (TKIs) has improved survival in this group of patients. Several generations of EGFR TKIs are currently available. The EGFR mutations have been divided into common and rare. The common mutations include Exon 19 deletion and Exon 21 L858R mutations and rest are grouped as rare. The presence of visceral metastasis in the brain and liver are usually portends a poor prognosis. Methods: We conducted a retrospective analysis of lung cancer patients who attended our hospital outpatient department from 2017 to 2021. The prevalence, demographics and clinical profile of EGFR common and rare mutations were studied using descriptive statistics. Survival of EGFR mutated patients was plotted using Kaplan Meier plots. SPSS was used for statistical analysis. Results: The prevalence of EGFR mutation among metastatic lung cancer was 14.10% (161/1148). The median age of the group was 60 years (23- 104 years). Smokers with EGFR mutations were 11.8% (n = 19). Male to Female ratios was 76:85 (47.2% and 52.8%). Three patients with squamous cell carcinoma exhibited EGFR mutation. Most common EGFR TKI used was Gefitnib. Osimertinib was used in 13 patients (1.4%). The percentage of common mutations were 85.75% (N = 132) and rare mutations were 14.3% (n = 22). The type of mutations could not be identified in 10 patients. The percentage of patients with exon 19 deletion were 63% (n = 97) and L858R were 24.7% (n = 38). Visceral metastasis (brain and liver) was seen in 47 patients (n = 29.2%). Brain progression was seen in 32 patients (n = 19.9%). The survival of patients with EGFR exon 19 deletion and L858R mutation was 16.36 + 8.97 months and 15.97+ 10.93 months, Survival among patients with common mutation was 16.20 + 9.57 months and among rare mutation was 13.43 + 12.19 months. Median Survival period of patients with visceral metastasis was 12 months (0 to 38 months). Conclusions: In our retrospective study, there was no significant difference between survival among common and rare EGFR mutations.

BackgroundCirculating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma.MethodsA total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples. EGFR mutation status in plasma samples were tested with ADx-SuperARMS EGFR assay and tumor tissue samples were tested with ADx-ARMS EGFR assay. The clinical sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) of ADx-SuperARMS EGFR assay were calculated by using EGFR mutation status in tumor tissue as standard reference. A receiver operating characteristic (ROC) analysis was implemented and an area under the curve (AUC) was calculated to evaluate sensitivity and specificity of exon 19 deletion (E19Del) and L858R mutation detection. The objective response rate (ORR) were calculated according to the EGFR mutation status determined by ADx-superARMS as well.Results0.2% analytical sensitivity and 100% specificity of the ADx-SuperARMS EGFR assays for EGFR E19Del, L858R, and T790M mutants were confirmed by using a series of diluted cell line DNA. In the clinical study, EGFR mutations were detected in 45.9% (50/109) of the plasma samples and in 56.9% (62/109) of the matched tumor tissue samples. The sensitivity, specificity, PPV and NPV of the ADx-SuperARMS EGFR assay for plasma EGFR mutation detection were 82.0% (50/61), 100% (48/48), 100% (50/50), and 81.4% (48/59), respectively. In ROC analysis, ADx-SuperARMS achieved sensitivity and specificity of 88% and 99% in E19Dels as well as sensitivity and specificity of 89% and 100% in L858R, respectively. Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease. The ORR and disease control rate (DCR) were 65.7% and 97.1%, respectively.ConclusionsADx-SuperARMS EGFR assay is likely to be a highly sensitive and specific method to noninvasively detect plasma EGFR mutations of patients with advanced lung adenocarcinoma. The EGFR mutations detected by ADx-SuperARMS EGFR assay could predict the efficacy of the treatment with first generation of EGFR-TKIs. Hence, EGFR blood testing with ADx-SuperARMS could address the unmet clinical needs.