Detection of EGFR mutations in NSCLC patients in clinical practice: Comparison between cobas and Scorpion ARMS method.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23101-e23101
Author(s):  
Natsuki Takano ◽  
Satoru Kitazono ◽  
Ryo Ariyasu ◽  
Junji Koyama ◽  
Masafumi Saiki ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Detection Rate ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Detection Rates ◽  
Initial Biopsy ◽  
Egfr Tki

e23101 Background: Epidermal growth factor receptor (EGFR) mutation is the most important factor for determining the treatment strategy for non-small-cell lung cancers (NSCLCs). Currently, two methods (cobas and Scorpion ARMS) have been approved as companion diagnostics for using EGFR tyrosine kinase inhibitor (TKI). Although there are some differences in the spectrums and sensitivities for detecting EGFRmutations such as exon 19 deletions (ex19del), L858R and T790M mutations, the extent of the differences affecting clinical practice is unclear. Methods: All patients with NSCLC who underwent EGFR mutation tests and treated at our hospital from February 2014 to February 2016 were enrolled. To detect EGFR mutations, the Scorpion ARMS (S) method was used from 2014 to 2015 and thecobasEGFR Mutation Test (C) from 2015 to 2016. We retrospectively investigated the detection rate of each EGFRmutation type and compared the rates between the two methods. Results: A total of 1,287 patients were enrolled. To detect EGFR mutations, 627 patients were tested by the S method and 660 by the C method, respectively. Of 1287 patients, 910 patients underwent initial biopsy, whereas 121 patients underwent re-biopsy after EGFR-TKI failure. EGFRmutations were detected in 130 of 418 (31.1%) patients and 153 of 492 (31.1%) patients by the S and C methods, respectively in the initial biopsy (P = 0.982). However, the detection rate of ex19del was slightly lower in the S method (12.6%) than in the C method (16.3%) (P = 0.105). Conversely, the detection rate of L858R was lower in the C method (13.8%) than in the S method (16.7%), but the difference was not significant (P = 0.252). De novo T790M was detected in one (0.2%) patient by the S method and in none by the C method. In re-biopsy after EGFR-TKI failure, the detection rates of T790M were as follows: 19 of 55 patients (34.5%) by the S method and 20 of 66 (30.3%) by the C method (P = 0.619). Conclusions: The different spectrums and sensitivities of EGFR mutations between the S and C methods were observed; however, they did not significantly affect clinical practice.

American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non–Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy

2011 ◽  
Vol 29 (15) ◽  
pp. 2121-2127 ◽  
Author(s):  
Vicki Leigh Keedy ◽  
Sarah Temin ◽  
Mark R. Somerfield ◽  
Mary Beth Beasley ◽  
David H. Johnson ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Mutation Testing ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
First Line Therapy ◽  
Egfr Tki ◽  
Egfr Mutation Testing

Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the clinical utility of using epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non–small-cell lung cancer (NSCLC) to predict the benefit of taking a first-line EGFR tyrosine kinase inhibitor (TKI). Clinical Context Patients with EGFR-mutated NSCLC have a significantly higher rate of partial responses to the EGFR TKIs gefitinib and erlotinib. In the United States, approximately 15% of patients with adenocarcinoma of the lung harbor activating EGFR mutations. EGFR mutation testing is widespread at academic medical centers and in some locales in community practice. As of yet, there is no evidence of an overall survival (OS) benefit from selecting treatment based on performing this testing. Recent Data One large phase III trial (the Iressa Pan-Asia Study [IPASS] trial), three smaller phase III randomized controlled trials using progression-free survival as the primary end point, and one small phase III trial with OS as the primary end point, all involving first-line EGFR TKIs and chemotherapy doublets, form the basis of this PCO. Provisional Clinical Opinion On the basis of the results of five phase III randomized controlled trials, patients with NSCLC who are being considered for first-line therapy with an EGFR TKI (patients who have not previously received chemotherapy or an EGFR TKI) should have their tumor tested for EGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriate first-line therapy. NOTE. ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.

scholarly journals Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis

2020 ◽  
Author(s):  
Bruce Feinberg ◽  
Balazs Halmos ◽  
Rasim Gucalp ◽  
Wenbo Tang ◽  
Barbara Moehring ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
De Novo ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Clinical Trial Registration ◽  
Evidence Based Treatment ◽  
Time To Treatment Failure ◽  
Epidermal Growth ◽  
Egfr Tki ◽  
Egfr T790m

Aim: To assess time-to-treatment failure (TTF) in US patients with epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib–osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0–34.1). Median overall survival was 47.6 months (90% CI: 35.5–51.5). Conclusion: Sequential afatinib–osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov)

EGFR mutation analysis and treatment outcomes with tyrosine kinase inhibitors in EGFR mutants: The Manchester Lung Cancer Group Experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18095-e18095
Author(s):  
Rahul Peck ◽  
Elizabeth Connolly ◽  
Paul Taylor ◽  
Corinne Faivre-Finn ◽  
Fiona Hellen Blackhall ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Smoking History ◽  
Egfr Mutations ◽  
Published Data ◽  
Duration Of Treatment

e18095 Background: The presence of Epidermal Growth Factor Receptor (EGFR) activating mutations in patients with NSCLC was first described in 2005. Tumours exhibiting these mutations show sensitivity to treatment with an oral Tyrosine Kinase Inhibitor. Testing for EGFR mutations in patients with non-squamous NSCLC began in the Greater Manchester and Cheshire network in the last quarter of 2009. Methods: We audited the notes of consecutive patients who were identified with an activating EGFR mutation by the Central Manchester Genetics Laboratory between November 2009 and October 2011. Results: A total of 110 mutations were identified in tumour tissue from 98 patients. 13.6% were in exon 18, 38.2% in exon 19, 15.4% in exon 20 and 32.8% in exon 21. 65% of patients were female. The median age was 69 years (36-89). Notes were available for 85 patients, 59 of whom received treatment with an EGFR TKi. 7 had previously received radical treatment and 19 never received treatment. 7% were current smokers, 40% were ex-smokers, 30.6% had never smoked and smoking history was not documented in 22.4%. An initial response to treatment was seen in 55%, with stable disease in 15%.The mean duration of treatment was 7.6 months (2 weeks – 23 months), with 24 patients still receiving a TKi at the time of data analysis. The most commonly seen toxicities were diarrhoea and rash. Only 1 patient had no documented toxicity from their TKi. 17 patients (29%) had treatment discontinued or interrupted because of toxicity. In 8 of these, treatment was re-introduced at a reduced dose, and 3 patients went back to full dose. Conclusions: Our results confirm that treatment with a TKi is effective for those patients whose tumours harbour EGFR mutations, with a side effect profile consistent with published data.

Small cell lung cancer (SCLC) among patients who are never smokers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7593-7593
Author(s):  
Anna M. Varghese ◽  
Helena Alexandra Yu ◽  
Helen H. Won ◽  
Camelia S. Sima ◽  
Gregory J. Riely ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Egfr Mutation ◽  
De Novo ◽  
Egfr Mutations ◽  
Kras Mutations ◽  
Lung Cancers ◽  
Never Smokers ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Generation Sequencing

7593 Background: Although most patients (pts) with SCLC are current or former smokers, SCLC has been reported in pts who are never smokers, most recently in pts with EGFR-mutant lung cancers who develop acquired resistance (AR) to EGFR tyrosine kinase inhibitors (TKIs). We describe clinical, pathologic, and molecular characteristics of never-smoking pts with SCLC at diagnosis and in the AR setting. Methods: We identified cases through systematic review of pts seen at MSKCC from 2005 – 2012. Smoking history was obtained prospectively. SCLC diagnosis was confirmed by expert pathology review. We collected age, sex, stage, treatment, and survival data. EGFR, KRAS, PIK3CA, and ALK testing and next generation sequencing of 279 cancer genes was performed on available samples. Results: 2.2% (23/1040, 95% CI 1.5 to 3.3%) of pts with SCLC seen at MSKCC were never smokers: 61% women, median 64 years, 74% extensive stage, and 22% with brain metastases at diagnosis. 83% (19/23) had de novo SCLC, whereas only 17% had SCLC as AR to EGFR TKI after treatment for EGFR-mutant lung cancers, all of whom had persistent EGFR mutation confirmed at resistance. Median survival from SCLC diagnosis is 23 months (95%CI: 11-26) for all pts and 23 months (95% CI: 8–27) for the 19 pts with de novo SCLC. Pathologic review demonstrated 19 cases of pure SCLC and 4 mixed histology cases with SCLC and other histologies. Treatment history was available for 15/19 pts with de novo SCLC: 53% etoposide-platinum sensitive. ALK rearrangement and KRAS mutations were identified in 0/5 and 0/10, respectively. One pt with de novo mixed SCLC and adenocarcinoma had an EGFR mutation and another pt with de novo pure SCLC had EGFR and PIK3CA mutations. Mutations were identified in p53 and Rb1 with amplification in TERT in 1 sample to date tested with next generation sequencing. Conclusions: 2% of pts with SCLC are never smokers. While transformation to SCLC can occur in the setting of AR to EGFR TKI, de novo SCLC occurs in the majority of our never smokers with this disease. EGFR mutations uniformly exist in SCLC in the AR setting. EGFR mutations were rare, and we found no KRAS mutations or ALK rearrangements. Comprehensive, multiplexed genotyping can aid in providing optimal care and facilitate research in this unique population.

scholarly journals Lung adenocarcinoma in a patient with Li–Fraumeni syndrome bearing a novel germ-line mutation, TP53R333Vfs*12

2020 ◽  
Vol 50 (10) ◽  
pp. 1214-1217 ◽  
Author(s):  
Shodai Takahashi ◽  
Kazuhiro Shimazu ◽  
Koya Kodama ◽  
Koji Fukuda ◽  
Taichi Yoshida ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Germ Line ◽  
Growth Factor Receptor ◽  
Triple Mutant ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
Egfr Tki

Abstract Germline mutations of TP53 are responsible for Li–Fraumeni syndrome in its 60–80%. We found a novel germline mutation, TP53: c.997del:p.R333Vfs*12 (NM_000546.6, GRCh, 17:7670713..7670713). The proband is a 40-year-old female, who was suffered from osteosarcoma in her right forearm at her age of 11. She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del). Her bone metastasis became resistant after 1-year treatment. Bone metastasis had an additional EGFR mutation (T790M). The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R333Vfs*12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.

Difference in incidence and pattern of salvage treatment after failure to first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy and standard cytotoxic chemotherapy in pts with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations: Okayama Lung Cancer Study Group experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7576-7576
Author(s):  
Yuka Kato ◽  
Eiki Ichihara ◽  
Katsuyuki Hotta ◽  
Akiko Hisamoto ◽  
Nagio Takigawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Cytotoxic Chemotherapy ◽  
Egfr Mutations ◽  
Deterioration Rate ◽  
Lung Cancer Study Group ◽  
Line Setting ◽  
To Receive ◽  
Egfr Tki

7576 Background: EGFR-TKI (E) therapy yielded a better PFS than standard cytotoxic chemotherapy (C) therapy and a comparable OS in untreated pts with EGFR-mt tumors, suggesting each of the treatments is now crucial for such subpopulation. But, it has not been fully evaluated yet which of each should be initiated first, and to what degree both of two are actually administered in early line setting in the treatment course. We here investigated a potential difference in incidence and pattern of delivery of subsequent crossover therapy after failure to each of the treatments in pts with EGFR-mt tumors. Methods: Consecutive 79 pts with advanced EGFR-mt NSCLC were retrospectively assessed who underwent E therapy (n = 39) or standard C therapy (n = 40) in the 1st-line setting between 2007 and 2011. Results: In E group 16 (41%) of 39 pts were still on 1st-line E therapy. Nine (39%) of the remaining 23 could not receive standard C therapy after failure to E therapy due to symptomatic CNS metastasis(mets) in 6, skeletal events in 2, and patient refusal in 1, whilst in C group only one (3%) of 40 failed to receive subsequent E therapy because of relapse (carcinomatous lymphangitis) (χ2-test; p < .001). Also, at the time of relapse to the 1-st line therapy, PS deteriorated more frequently in E group (8/23 vs. 7/40; p = .042) and, relapse with symptomatic CNS mets seemed frequently observed in E group (6/23 vs. 4/40; p = .093). Multivariate analysis revealed type of regimens undergone in the 1st-line setting (E vs. C) correlated with failure of administration of subsequent crossover therapy (odd ratio: 3.224, 95%CI: .1.032 – 5,417, p = .004). Conclusions: It seems that pts with EGFR-mt tumors who were treated with 1st-line C had better opportunity to receive post-progression E therapy than those treated with 1st-line E had chance to receive subsequent C therapy, possibly due to difference in PS deterioration rate and relapse pattern.

The efficacy and toxicity of osimertinib in T790M-positive NSCLC with acquired resistance to EGFR-TKI in clinical practice.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20575-e20575 ◽  
Author(s):  
Tomoaki Sonoda ◽  
Noriko Yanagitani ◽  
Masafumi Saiki ◽  
Ryo Ariyasu ◽  
Junji Koyama ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Cns Metastasis ◽  
Grade 3 ◽  
Egfr Tki

e20575 Background: A Phase III study (AURA3) demonstrated that osimertinib prolonged PFS compared to platinum doublet in patients with T790M-positive non-small-cell lung cancer (NSCLC) exhibiting acquired resistance to epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI). Although the patients in the study had good PS and only one prior EGFR-TKI treatment, most practical patients had multiple prior EGFR-TKI and poor PS. Moreover, several patients exhibited symptomatic central nervous system (CNS) metastasis in clinical practice. In this study, we evaluated the efficacy and toxicity of osimertinib in clinical practice. Methods: We retrospectively analyzed 30 patients who were treated with osimertinib at our hospital from April 11th 2016 to September 30th 2016. The efficacy and toxicity was compared between the patients with matched and unmatched AURA3 eligibility criteria. Efficacy was evaluated according to RECIST ver.1.1 and toxicity was evaluated using CTCAE ver.4.0. Results: A total of 9 out of 30 patients matched the AURA3 eligibility criteria (PS ≤ 1 and one prior EGFT-TKI) and 21 patients were unmatched (PS ≥ 2 or two or more EGFR-TKI or symptomatic CNS metastasis). The overall response rate(ORR) of osimertinib was 78% and 67% for the matched and unmatched patients, respectively. The disease control rate (DCR) was 100% and 90% for the matched and unmatched patients, respectively. In addition, the response rate of symptomatic CNS metastasis was 67%. Regarding toxicity, grade 3/4 toxicities were observed in 22% of the matched patients and 33% of the unmatched patients. In the matched patients, the most frequent AE was a rash (89%) and the frequent grade 3/4 toxicities were a rash (22%) and pneumonitis (11%). In unmatched patients, the most frequent AE was also a rash (57%), but the frequent grade 3/4 toxicities were pneumonitis (14%), rash (10%), and neutropenia (10%). Conclusions: Both the ORR and DCR in the unmatched patients were slightly lower than the matched patients; however, osimertinib was still found to be beneficial in clinical practice.

How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitor for lung adenosquamous cell carcinoma harboring EGFR mutation? A bicenter research and pooled analysis of published reports.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20571-e20571
Author(s):  
Yong-Mei Liu ◽  
Xueming Xia ◽  
Wei Du ◽  
Yan Zhang ◽  
Jianlin Xu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Receptor Tyrosine Kinase ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Pooled Analysis ◽  
Epidermal Growth ◽  
Egfr Tki

e20571 Background: Lung adenosquamous cell carcinoma (ASC) is a rare subtype of lung cancer. Little is known about the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung ASC with EGFR mutation. Methods: We retrospectively analyzed 44 patients with advanced or recurrent lung ASC harboring EGFR mutation who were treated with EGFR-TKI from two cancer centers to investigate the efficacy. Then a pooled analysis on the efficacy of EGFR-TKI was performed in 74 patients including 30 patients selected from 11 published reports. Results: In our bicenter research, for the ASC patients treated with EGFR-TKI, the objective response rate (ORR), the disease control rate (DCR), the median progression free survival (mPFS) and the median overall survival (mOS) were 54.5%, 79.5%, 8.8 months and 19.43 months, respectively. In pooled analysis, the ORR, DCR, mPFS and mOS of ASC patients were 63.4%, 85.9%, 10.00 months and 21.37 months, respectively. Similar PFS (11.0 vs. 10.0 months; P= 0.771) and OS (23.67 vs. 20.33 months; P= 0.973) were found in patients with deletion in exon 19 and exon 21 L858R mutation. The patients treated with erlotinib or gefitinib had a trend of better OS than those treated with icotinib. Conclusions: EGFR-TKI is an effective treatment for ASC harboring EGFR mutation, comparing with historical data, similar to EGFR-mutated adenocarcinoma (ADC). Further study is needed to identify the different role of the two components of ASC in EGFR treatment.

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