Consensus for EGFR Mutation Testing in Non-small Cell Lung Cancer: Results from a European Workshop

Pirker, Robert; Herth, Felix J.F.; Kerr, Keith M.; Filipits, Martin; Tarón, Miquel; Gandara, David R.; Hirsch, Fred R.; Grunenwald, Dominique; Popper, Helmut; Smit, Egbert F.; Dietel, Manfred; Marchetti, Antonio; Manegold, Christian; Stella, Péter; Thomas, Michael; Rosell, Rafael; Cappuzzo, Federico; Stahel, Rolf A.

doi:10.1097/jto.0b013e3181f1c8de

Cited by 259 publications

(261 citation statements)

References 42 publications

Supporting

Mentioning

224

Contrasting

Unclassified

Order By: Relevance

“…It was suggested that EGFR mutation testing is routinely performed in patients with lung adenocarcinoma in most countries (27)(28)(29). However, a number of NSCLC patients harboring EGFR mutations, who would potentially benefit from EGFR-TKI treatment (gefitinib or erlotinib) may be precluded if the decision to perform EGFR mutation testing is based solely on histological subtype, gender and smoking status.…”

Section: Egfr Mutation Testingmentioning

confidence: 99%

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Hsiao¹,

Lin

Chou

et al. 2013

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Mutations in epidermal growth factor receptor (EGFR) commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for EGFR mutations in NSCLC. To elucidate the confounding effect, Pearson's χ 2 test and logistic regression models were used to correlate these characteristics with EGFR mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P<0.001)] and adenocarcinoma (OR=9.43, 95% CI 3.62-24.56; P<0.001) were associated with EGFR mutations; however, gender was not (OR=1.25, 95% CI: 0.73-2.15; P=0.416). Furthermore, gender was not associated with EGFR mutation subtypes (OR=1.19, 95% CI: 0.56-2.50; P=0.650). The frequency of EGFR mutations among females and males was not different in non-smokers (64.8 vs. 55.8%, P=0.204) or ever-smokers (27.8 vs. 24.2%, P=0.775). Therefore, if the assessment for EGFR mutation status was limited to non-smoking females with adenocarcinoma, up to 40% of the patients harboring EGFR mutations would be precluded from the benefit of EGFR inhibitor therapy. Our results indicated that gender is a confounding factor for EGFR mutations in NSCLC and suggested that gender may not be associated with tumorigenesis in NSCLC-harboring EGFR mutations.

show abstract

Section: Egfr Mutation Testingmentioning

confidence: 99%

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Hsiao¹,

Lin

Chou

et al. 2013

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…Fortunately, most FNA procedures routinely have either a concurrent biopsy or a follow-up surgical excision, which provide adequate tissue for molecular assessment. 10,11 In some instances, however, cytological specimens may be the only material available for molecular testing. If the tumor is locally advanced or metastatic, surgical resection is not performed.…”

mentioning

confidence: 99%

Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics

et al. 2014

View full text Add to dashboard Cite

Increasing use of fine needle aspiration for oncological diagnosis, while minimally invasive, poses a challenge for molecular testing by traditional sequencing platforms due to high sample requirements. The advent of affordable benchtop next-generation sequencing platforms such as the semiconductor-based Ion Personal Genome Machine (PGM) Sequencer has facilitated multi-gene mutational profiling using only nanograms of DNA. We describe successful next-generation sequencing-based testing of fine needle aspiration cytological specimens in a clinical laboratory setting. We selected 61 tumor specimens, obtained by fine needle aspiration, with known mutational status for clinically relevant genes; of these, 31 specimens yielded sufficient DNA for next-generation sequencing testing. Ten nanograms of DNA from each sample was tested for mutations in the hotspot regions of 46 cancer-related genes using a 318-chip on Ion PGM Sequencer. All tested samples underwent successful targeted sequencing of 46 genes. We showed 100% concordance of results between next-generation sequencing and conventional test platforms for all previously known point mutations that included BRAF, EGFR, KRAS, MET, NRAS, PIK3CA, RET and TP53, deletions of EGFR and wild-type calls. Furthermore, next-generation sequencing detected variants in 19 of the 31 (61%) patient samples that were not detected by traditional platforms, thus increasing the utility of mutation analysis; these variants involved the APC, ATM, CDKN2A, CTNNB1, FGFR2, FLT3, KDR, KIT, KRAS, MLH1, NRAS, PIK3CA, SMAD4, STK11 and TP53 genes. The results of this study show that next-generation sequencing-based mutational profiling can be performed on fine needle aspiration cytological smears and cell blocks. Next-generation sequencing can be performed with only nanograms of DNA and has better sensitivity than traditional sequencing platforms. Use of next-generation sequencing also enhances the power of fine needle aspiration by providing gene mutation results that can direct personalized cancer therapy.

show abstract

“…Technical aspects of EGFR testing are beyond our scope 51 ; however, microdissection and sequencing (Figure 1) may represent the current clinical standard. Allele-specific amplification-for example, Scorpions ARMS (DxS Limited, Manchester, U.K.)-is an alternative.…”

Section: Egfrmentioning

confidence: 99%

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

et al. 2012

View full text Add to dashboard Cite

New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-smallcell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers.The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest.Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents.These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies.

show abstract

Consensus for EGFR Mutation Testing in Non-small Cell Lung Cancer: Results from a European Workshop

Abstract: The recommendations of the workshop will help implement EGFR mutation testing in Europe and, thereby, optimize the use of EGFR-TKIs in clinical practice.

Cited by 259 publications

References 42 publications

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

Contact Info

Product

Resources

About