Comprehensive cross‐platform comparison of methods for non‐invasive EGFR mutation testing: results of the RING observational trial

e20507 Background: It is reported that about 20% of patients with resected NSCLC adenocarcinoma harbor an EGFR driver mutation in the United States. Up to the recent approval of osimertinib in the adjuvant setting for resected EGFR + NSCLC based on the ADAURA trial, routine molecular profiling of early-stage lung cancer had not been standard of care. We hypothesize that there is a significant proportion of patients with resected adenocarcinoma with unknown EGFR status who could benefit from treatment that are missed with our current testing practices. Methods: We performed a retrospective analysis of Stage IB-IIIA lung adenocarcinomas resected at the University of Miami from 2014 to 2019. Eligible patients were identified from the Cancer Registry and information on EGFR mutation testing and treatment was obtained from chart review. We evaluated the prevalence of EGFR mutation testing in this population and outcomes based on EGFR mutation status. Disease free survival (DFS) and clinico-pathologic characteristics were evaluated. We estimated the number of patients that would have been eligible for EGFR testing and adjuvant osimertinib therapy in the pre-ADAURA era in our patient cohort. Results: A total of 120 patients had resected stage IB-IIIA adenocarcinoma during this five-year period (Stage IB 42.5%; Stage IIA 13.3%; Stage IIB 25%; Stage IIIA 19.2%) with a median age of 66 years. Most were females (59%), NHWs (51.5%), Hispanics (46.9%), and former smokers (66.7%). Out of patients with Stage IB-IIIA NSCLC with adenocarcinoma, 42.5% completed recommended adjuvant platinum-based chemotherapy. Only 40% of patients were referred for EGFR testing during this study period. The prevalence of EGFR mutations in this population was 10.8% (13 /120), but 59% of cases had no available EGFR testing. The most prevalent mutation was L858R (53.8%) followed by exon-19 deletions (30.8%). A total of 6 patients received an EGFR TKI therapy during the follow up period (2 in the adjuvant setting). With a median follow up of 12 mos, the rate of recurrence by stage was: Stage IB (3.9%); Stage IIB (10%); Stage IIIA (13%). Median time to disease progression or death was 13 months in this subgroup. There was no difference in disease free survival for patients with EGFR testing and those without results available in this short follow up period. Conclusions: Based on this retrospective review, up to 60% of patients with early-stage NSCLC with non-squamous histology have no available EGFR testing in the pre-ADAURA era. Of the anticipated 20% of patients with expected EGFR mutations based on historical controls, we have only identified half of patients that would have been eligible for adjuvant osimertinib. This study establishes the importance of upfront EGFR mutation testing in all NSCLC patients, not only to prognosticate, but also to identify the subset of patients who could benefit from adjuvant EGFR therapy.

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Implementation Of EGFR Mutation Testing In Antwerp, Belgium: The HERMES-Project

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2523 ◽

2012 ◽

Author(s):

Paul Germonpre ◽

Els De Droogh ◽

Anneke Lefebure ◽

Mark Kockx ◽

Patrick Pauwels ◽

...

Keyword(s):

Egfr Mutation ◽

Mutation Testing ◽

Egfr Mutation Testing

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Abstract D134: Patterns of EGFR mutation testing among patients with metastatic lung cancer in a safety-net hospital

10.1158/1538-7755.disp19-d134 ◽

2020 ◽

Author(s):

Ana I Velazquez ◽

Niharika Dixit

Keyword(s):

Lung Cancer ◽

Egfr Mutation ◽

Safety Net ◽

Mutation Testing ◽

Metastatic Lung Cancer ◽

Safety Net Hospital ◽

Metastatic Lung ◽

Egfr Mutation Testing

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Clinical recommendations for EGFR mutation testing in non-small cell lung cancer (NSCLC): Results from a European workshop.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.e18038 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. e18038-e18038

Author(s):

R. Pirker ◽

F. Herth ◽

K. M. Kerr ◽

M. Filipits ◽

D. Grunenwald ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Mutation Testing ◽

Small Cell ◽

Small Cell Lung ◽

Clinical Recommendations ◽

European Workshop ◽

Egfr Mutation Testing

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Population-based pan-Canadian EGFR-mutation testing program.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e18017 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e18017-e18017 ◽

Cited By ~ 1

Author(s):

M. S. Tsao ◽

D. Ionescu ◽

G. Chong ◽

A. M. Magliocco ◽

D. Soulieres ◽

...

Keyword(s):

Egfr Mutation ◽

Population Based ◽

Mutation Testing ◽

Testing Program ◽

Egfr Mutation Testing

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Retrospective EGFR mutation testing of clinical specimens from the EURTAC trial of erlotinib in non-small cell lung cancer (NSCLC) using a novel allele-specific PCR (AS-PCR) assay.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10596 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10596-10596 ◽

Cited By ~ 1

Author(s):

Susana Benlloch ◽

Miquel Taron ◽

Maria Luisa Botero ◽

Jordi Bertran-Alamillo ◽

Clara Mayo ◽

...

Keyword(s):

Tumor Cells ◽

Sanger Sequencing ◽

Egfr Mutation ◽

Mutation Testing ◽

Pcr Assay ◽

Percent Agreement ◽

Egfr Mutant ◽

Laser Capture ◽

Egfr Mutation Testing ◽

Exon 19

10596 Background: Anti-EGFR inhibitors are superior to chemotherapy in first-line therapy of advanced EGFR-mutant NSCLC. The EURTAC trial was a randomized Phase III trial of erlotinib vs. chemotherapy in patients with EGFR-mutant NSCLC. Interim results showed significant improvement in progression-free survival (R. Rosell, ASCO 2011). An accurate rapid in vitro diagnostic for EGFR mutations is needed to select patients for this therapy. Methods: Prospective EGFR mutation testing for the trial was performed on laser-capture microdissected tumor cells using a combination of 3 lab-developed tests (LDTs), including a Length Analysis of Fluorescently-labeled PCR (Genescan) method for exon 19 deletions, a Taqman-based PCR assay for exon 21 mutation with laser-capture macrodissected tumor cells, and secondary Sanger sequencing. A subset of samples from the trial was retrospectively tested with an AS-PCR assay (cobas EGFR mutation test) which detects L858R and > 29 exon 19 deletions. The test provides automated results within 8 h; the DNA required can be isolated from one 5-micron tissue section. Four methods were compared: AS-PCR assay, LDT, direct Sanger sequencing and massively parallel sequencing (MPS; 454, Branford, CT). Results: LDT results were obtained for 1044 screened patients. Residual tumor blocks were available for 487 patients (47%), including 303 wild-type, 172 mutant (135 enrolled on the trial) and 12 inconclusive cases by the LDT. Comparison of AS-PCR and LDT results showed a positive percent agreement (PPA) – 93.7% (CI 88.8%, 96.5%), and negative percent agreement (NPA) – 97.5% (94.9%, 98.8%). Comparison of AS-PCR and Sanger results showed a PPA of 96.6% (91.7%, 98.7%) but an NPA of 88.3% (84.1%, 91.5%). Among 34 AS-PCR+/Sanger- case, MPS confirmed the presence of exon 19 deletions in 25 cases and L858R mutations in 7. Direct comparison of AS-PCR and MPS results showed a PPA of 93.1% (88.1%, 96.1%) and NPA of 97.7% (95.0%, 98.9%). Clinical outcomes for cases with mutations detected by the AS-PCR test will be presented. Conclusions: The AS-PCR assay was highly concordant with the LDT and MPS, and more sensitive than Sanger sequencing.

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8054 ◽

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.

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