Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

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P3.13-16 Concomitant EML4-ALK Rearrangement and EGFR Mutation in Non-Small Cell Lung Cancer Patients: Data from Eastern Indian Hospital.

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.1856 ◽

2018 ◽

Vol 13 (10) ◽

pp. S982

Author(s):

P. Mohapatra ◽

S. Bhuniya ◽

M. Panigrahi ◽

S. Patra ◽

P. Mishra ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Alk Rearrangement ◽

Lung Cancer Patients

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Diagnostic Accuracy of Noninvasive Genotyping of EGFR in Lung Cancer Patients by Deep Sequencing of Plasma Cell-Free DNA

Clinical Chemistry ◽

10.1373/clinchem.2015.241414 ◽

2015 ◽

Vol 61 (9) ◽

pp. 1191-1196 ◽

Cited By ~ 66

Author(s):

Junji Uchida ◽

Kikuya Kato ◽

Yoji Kukita ◽

Toru Kumagai ◽

Kazumi Nishino ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Deep Sequencing ◽

Limit Of Detection ◽

Detection System ◽

Egfr Mutations ◽

Plasma Dna ◽

Lung Cancer Patients ◽

Therapeutic Decisions ◽

Exon 19

Abstract BACKGROUND Genotyping of EGFR (epidermal growth factor receptor) mutations is indispensable for making therapeutic decisions regarding whether to use EGFR tyrosine kinase inhibitors (TKIs) for lung cancer. Because some cases might pose challenges for biopsy, noninvasive genotyping of EGFR in circulating tumor DNA (ctDNA) would be beneficial for lung cancer treatment. METHODS We developed a detection system for EGFR mutations in ctDNA by use of deep sequencing of plasma DNA. Mutations were searched in >100 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. We conducted a multi-institute prospective study to evaluate the detection system, enrolling 288 non–small cell lung cancer (NSCLC) patients. RESULTS In evaluating the performance of the detection system, we used the genotyping results from biopsy samples as a comparator: diagnostic sensitivity for exon 19 deletions, 50.9% (95% CI 37.9%–63.9%); diagnostic specificity for exon 19 deletions, 98.0% (88.5%–100%); sensitivity for the L858R mutation, 51.9% (38.7%–64.9%); and specificity for L858R, 94.1% (83.5%–98.6%). The overall sensitivities were as follows: all cases, 54.4% (44.8%–63.7%); stages IA–IIIA, 22.2% (11.5%–38.3%); and stages IIIB–IV, 72.7% (60.9%–82.1%). CONCLUSIONS Deep sequencing of plasma DNA can be used for genotyping of EGFR in lung cancer patients. In particular, the high specificity of the system may enable a direct recommendation for EGFR-TKI on the basis of positive results with plasma DNA. Because sensitivity was low in early-stage NSCLC, the detection system is preferred for stage IIIB–IV NSCLC.

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P3.02b-026 Association of EGFR Exon 19 Deletion and EGFR-TKI treatment duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2016.11.1693 ◽

2017 ◽

Vol 12 (1) ◽

pp. S1201-S1202

Author(s):

Norikazu Matsuo ◽

Koichi Azuma ◽

Kazuko Sakai ◽

Akihiko Kawahara ◽

Hidenobu Ishii ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Treatment Duration ◽

T790m Mutation ◽

Lung Cancer Patients ◽

Exon 19 Deletion ◽

Tki Treatment ◽

Egfr Mutant ◽

Egfr Tki ◽

Exon 19

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Analytical Validation of a Pan-Cancer Panel for Cell-Free Assay for the Detection of EGFR Mutations

Diagnostics ◽

10.3390/diagnostics11061022 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1022

Author(s):

Min-Kyung So ◽

Jong-Ho Park ◽

Jong-Won Kim ◽

Ja-Hyun Jang

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Reference Materials ◽

Egfr Mutation ◽

Egfr Mutations ◽

Advanced Lung Cancer ◽

Clinical Samples ◽

Lung Cancer Patients ◽

Pan Cancer

Liquid biopsies have increasingly shown clinical utility. Although next-generation sequencing has been widely used for the detection of somatic mutations from plasma, performance characteristics vary by platform. Therefore, thorough validation is mandatory for clinical use. This study aimed to evaluate the analytical validity of the Oncomine Pan-Cancer Cell-Free Assay. A massively parallel sequencing for the assay was performed using the Ion S5 XL System with Ion 540 kit. The analytical sensitivity and precision were evaluated using pre-characterized reference materials. The specificity was evaluated using plasma from healthy subjects. A comparison with the Cobas EGFR Mutation Test v2 was performed using reference materials and plasma from lung cancer patients. For SNVs and short indels, the analytical sensitivities at variant allele frequencies (VAFs) of 0.1%, 0.5%, and 1% were 50%, 93.4%, and 100% with 20 ng of input, respectively. The overall precision of the true positive variants was 98% at a VAF of 1% with 20 ng input. The assay showed a similar sensitivity to that of the Cobas EGFR Mutation Test v2 at a VAF of 0.5% with 20 ng of input and 100% concordance on clinical samples. The Pan-Cancer Cell-Free Assay can be applied to detect EGFR mutations in advanced lung cancer patients, although follow-up studies will be needed to evaluate the analytical validity for other types of genes and aberrations using clinical samples.

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Incidence, characteristics, and survival of patients with EGFR-mutant lung cancers with EGFR T790M at diagnosis identified in the lung cancer mutation consortium (LCMC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8085 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8085-8085

Author(s):

Mark G. Kris ◽

Geoffrey R. Oxnard ◽

Bruce E. Johnson ◽

Lynne D Berry ◽

Heidi Chen ◽

...

Keyword(s):

Lung Cancer ◽

Egfr Mutation ◽

Acquired Resistance ◽

Stage Iv ◽

Egfr Mutations ◽

Lung Cancers ◽

Exon 20 ◽

Egfr Mutant ◽

Egfr T790m ◽

Exon 19

8085 Background: Somatic T790M mutations are detected in 62% of EGFR-mutant lung cancers with acquired resistance to EGFR TKIs, and have rarely been identified in the tumor at diagnosis and/or within the germline DNA. Multiplexed genotyping by the LCMC permitted us to evaluate the incidence of T790M at diagnosis, co-mutations, and survival of patients with this driver. Methods: The 14 member LCMC prospectively tested tumors of patients with lung adenocarcinomas in CLIA laboratories for mutations in EGFR and 9 other genes. We assayed T790Mby Sequenom, Snapshot, or Sanger sequencing. Germline DNA was not collected. Results: In the 987 tumors tested, 209 had mutations in EGFR alone: 25 T790M (2.5%) , 157 sensitizing EGFR mutations (exon 19 del, L858R, L861Q, G719X) without T790M, 23 exon 20 ins, 4 other mutations. 13 additional cases harbored mutations in EGFR and another driver; 2 with both T790M and PIK3CA. In each of the 27 EGFR-mutant cases with T790M, a coincident EGFR mutation was detected (18 exon 19 del, 9 L858R, 1 exon 20 ins). EGFR T790M was found more often than EGFR exon 20 ins or mutations in HER2 (1.9%), BRAF (1.6%), or PIK3CA (0.7%). Patients with T790M: 77% women, 81% never smokers, median age 55 (range 38-79), stage IV at diagnosis 81%, PS 0/1 100%. Characteristics did not differ from persons with sensitizing mutations and no T790M. Median survival from the diagnosis of metastatic disease for patients with EGFR-mutant lung cancers was 3.5 yrs with T790Mand 4.0 yrs without (p=0.926). Conclusions: T790M mutations were detected at diagnosis in 3% of adenocarcinomas and always coincident with another EGFR mutation. Cases with T790M represent 13% of all cases of EGFR- mutant lung cancer. Characteristics and survival for patients with EGFR- mutant lung cancers with T790M at diagnosis were similar to individuals with sensitizing mutations and no T790M. The observed incidence of T790M exceeded that of the other actionable targets HER2, BRAF, and PIK3CA. Trials should study this unique population identified by routine multiplexed genotyping. Supported by 1RC2CA148394-01 and the National Lung Cancer Partnership. Clinical trial information: NCT01014286.

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Determination of plasma EGFR mutations from non-small cell lung cancer patients at Bach Mai Hospital.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13121 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13121-e13121

Author(s):

Cam Phuong Pham ◽

Khoa Trong Mai ◽

Nguyen Thuan Loi ◽

NGO Thi Thu Hien ◽

Quynh Thi Thuy Vo ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

T790m Mutation ◽

Lung Cancer Patients

e13121 Background: Lung cancer patients with mutations in the epidermal growth factor receptor (EGFR) are primary candidates for EGFR-targeted therapy. Reliable analyses of such mutations have previously been possible only in tumor tissue. Here, we demonstrate that mutations can be detected in plasma samples of non-small cell lung cancer patients at Bach Mai Hospital and relation of different variables to the frequency of EGFR mutations. Methods: 193 patients with non-small cell lung cancer were identified with EGFR mutation by cobas EGFR Mutation Test v2 kit (Roche Diagnostics, USA), evaluating the EGFR mutation status with different variables. Results: The EGFR mutation rate was 43%, common in patients with adenocarcinoma, female, non-smoking, late stage disease. The rate of EGFR T790M mutation was 36.1%. Among 78 patients who was previous treated TKIs, EGFR mutation rate was 73.1% and the rate of EGFR T790M mutation was 50.8% at the time of progression. The concordance of EGFR mutation from plasma sample with tissue sample was 81%. Conclusions: EGFR mutation in plasma sample results was not different from those in tissue samples and similar with result of studies in Vietnam and worldwide.

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