Epidermal growth factor receptor mutation frequency and non-small cell lung cancer management: implication for treatment choices

Mello, Ramon Andrade de; Araújo, António

doi:10.6061/clinics/2012(11)22

Cited by 4 publications

(4 citation statements)

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“…This result may be explained by ethnic differences among the study populations. Our study used a predominantly Portuguese population, and a heterogeneous European population was involved in the EXTREME trial [15] , [21] – [24] . In addition, SCCHN tumors are rich in EGFR, which may explain the high sensitivity to anti-EGFR therapies [25] .…”

Section: Discussionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) pathways were shown in previous pre-clinical studies to have a major role in SCCHN carcinogenesis by regulating p53 and Rb gene expression. p53 and Rb are regulators of cell cycle control, cell proliferation and apoptosis [14] , [15] . More recently, cetuximab, an IgG1 monoclonal antibody against the extracellular portion of the epidermal growth factor receptor (EGFR), was extensively studied in this field [9] , [13] , [16] .…”

Section: Introductionmentioning

confidence: 99%

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Cetuximab Plus Platinum-Based Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Retrospective Study in a Single Comprehensive European Cancer Institution

et al. 2014

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BackgroundThe use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort.Patients and MethodsThis study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first.ResultsThe median patient age was 53 (37–78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684–13.316) and PFS of 8 months (CI 95%, 6.051–9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%).ConclusionsThe results of this study suggest that cetuximab plus platinum–fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cetuximab Plus Platinum-Based Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Retrospective Study in a Single Comprehensive European Cancer Institution

et al. 2014

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“…EGFR mutations in exons 19 and 21 are the most effective, predictive biomarkers of the response to EGFR TKIs for first-line advanced NSCLC treatment [37], [38]. In this context, finding novel predictive biomarkers for overall systemic treatment remains a challenge for clinicians and researchers.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

et al. 2013

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IntroductionPolymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population.Materials and MethodsBlood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS).ResultsOne hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029.ConclusionsOur study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.

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“…Another study found a lower rate of EGFR mutation of 21.6% in a cohort of 125 Brazilian patients. Deletions in Exon 19 (75%), followed by the point mutation of Exon 21 (25%), were also the most common mutations . The frequency of EGFR mutations across different countries in Latin America has also been studied.…”

Section: Introductionmentioning

confidence: 99%

EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil

et al. 2018

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Background. In Brazil, cancer is the second most common cause of death. Most patients in resource-limited countries are diagnosed in advanced stages. Current guidelines advocate for EGFR mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of EGFR testing and the changes in patterns of testing overtime. Materials and Methods. This was an observational, retrospective study. We obtained deidentified data from a commercial database, which included 11,684 patients with non-small cell lung cancer treated between 2011 and 2016 in both public and private settings. We analyzed the frequency of EGFR mutation testing over time. We also directly studied 3,664 tumor samples, which were analyzed between 2011 and 2013. These samples were tested for EGFR mutations through an access program to tyrosine kinase inhibitors in Brazil.Results. Overall, 38% of patients were tested for EGFR mutations; 76% of them were seen in the private sector, and 24% were seen in the public center. The frequency of testing for EGFR mutations increased significantly over time: 13% (287/2,228 patients) in 2011, 34% (738/2,142) in 2012, 39% (822/2,092) in 2013, 44% (866/1,972) in 2014, 53% (1,165/2,184) in 2015, and 42% (1,359/3,226) in 2016. EGFR mutations were detected in 25.5% of analyzed samples (857/3,364). Deletions in Exon 19 were the most frequent mutations, detected in 54% of patients (463/857). Conclusion. Our findings suggest that the frequency of EGFR mutation in this cohort was lower than that found in Asia but higher than in North American and Western European populations. The most commonly found mutations were in Exon 19 and Exon 21. Our study shows that fewer than half of patients are being tested and that the disparity is greater in the public sector. The Oncologist 2019;24:e137-e141 Implications for Practice: These data not only indicate the shortage of testing but also show that the rates of positivity in those tested seem to be higher than in other cohorts for which data have been published. This study further supports the idea that awareness and access to testing should be improved in order to improve survival rates in lung cancer in Brazil.

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Epidermal growth factor receptor mutation frequency and non-small cell lung cancer management: implication for treatment choices

Cited by 4 publications

References 6 publications

Cetuximab Plus Platinum-Based Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Retrospective Study in a Single Comprehensive European Cancer Institution

Cetuximab Plus Platinum-Based Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Retrospective Study in a Single Comprehensive European Cancer Institution

The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil

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