148P: Concordance between detection of EGFR mutations on tissue and in circulating free tumor DNA (cftDNA) in newly diagnosed metastatic lung adenocarcinoma (mLA)

Abstract Background Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. Methods We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. Results A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p < 0.0001). Conclusion Patients receiving 30 mg afatinib daily as their initial treatment had similar RR, PFS, OS, but significantly fewer serious ADRs, as compared with those using 40 mg as their starting dose.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21615 ◽

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]

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Analysis of Progression Patterns and Failure Sites of Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations Receiving First-line Treatment of Tyrosine Kinase Inhibitors

Clinical Lung Cancer ◽

10.1016/j.cllc.2020.04.004 ◽

2020 ◽

Vol 21 (6) ◽

pp. 534-544 ◽

Cited By ~ 1

Author(s):

Xiao-yang Li ◽

Xue-ru Zhu ◽

Chen-chen Zhang ◽

Wen Yu ◽

Bo Zhang ◽

...

Keyword(s):

Tyrosine Kinase ◽

Lung Adenocarcinoma ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Egfr Mutations ◽

Line Treatment ◽

First Line ◽

Metastatic Lung ◽

First Line Treatment ◽

Progression Patterns

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Somatic Copy-Number Alterations in Plasma Circulating Tumor DNA from Advanced EGFR-Mutated Lung Adenocarcinoma Patients

Biomolecules ◽

10.3390/biom11050618 ◽

2021 ◽

Vol 11 (5) ◽

pp. 618

Author(s):

Anna Buder ◽

Ellen Heitzer ◽

Julie Waldispühl-Geigl ◽

Sabrina Weber ◽

Tina Moser ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Copy Number ◽

Circulating Tumor Dna ◽

Egfr Mutations ◽

Genomic Profiling ◽

Plasma Samples ◽

Copy Number Alterations ◽

Egfr Mutated ◽

Tumor Dna ◽

Somatic Copy Number Alterations

Background: To assess the clinical relevance of genome-wide somatic copy-number alterations (SCNAs) in plasma circulating tumor DNA (ctDNA) from advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma patients. Methods: We included 43 patients with advanced EGFR T790M-positive lung adenocarcinoma who were treated with osimertinib after progression under previous EGFR-TKI therapy. We performed genomic profiling of ctDNA in plasma samples from each patient obtained pre-osimertinib and after patients developed resistance to osimertinib. SCNAs were detected by shallow whole-genome plasma sequencing and EGFR mutations were assessed by droplet digital PCR. Results: SCNAs in resistance-related genes (rrSCNAs) were detected in 10 out of 31 (32%) evaluable patients before start of osimertinib. The presence of rrSCNAs in plasma before the initiation of osimertinib therapy was associated with a lower response rate to osimertinib (50% versus 81%, p = 0.08) and was an independent predictor for shorter progression-free survival (adjusted HR 3.33, 95% CI 1.37–8.10, p = 0.008) and overall survival (adjusted HR 2.54, 95% CI 1.09–5.92, p = 0.03). Conclusions: Genomic profiling of plasma ctDNA is clinically relevant and affects the efficacy and clinical outcome of osimertinib. Our approach enables the comprehensive assessment of SCNAs in plasma samples of lung adenocarcinoma patients and may help to guide genotype-specific therapeutic strategies in the future.

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A Case Report of EGFR-mutated Metastatic Lung Adenocarcinoma with Long-term Survival on Systemic Treatment

Journal of Medical and Radiation Oncology ◽

10.53011/jmro.2021.01.05 ◽

2021 ◽

Vol 1 (1) ◽

pp. 51-58

Author(s):

Daniel Dulf ◽

Paul Kubelak ◽

Dana Iancu ◽

Tudor-Eliade Ciuleanu

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutations ◽

Term Survival ◽

Metastatic Lung ◽

Cellular Pathways ◽

Long Term Survivors ◽

Egfr Mutated ◽

Egfr Tkis ◽

Systemic Therapies

"Metastatic non-small cell lung cancer has historically been associated with a poor prognosis. The introduction of targeted agents against certain molecules involved in cellular pathways has shown improved responses, but long-term survivors are still rare. We present the case of a patient with lung adenocarcinoma harboring sensitizing EGFR mutations who showed an impressive survival of more than 9 years following a combination of systemic therapies consisting of cytotoxic drugs and EGFR TKIs that were very well tolerated."

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