Share This Article:

Frequency of Epidermal Growth Factor Mutation Status and Its Effect on Outcome of Patients with Adenocarcinoma of the Lung

Abstract Full-Text HTML Download Download as PDF (Size:2687KB) PP. 1012-1020
DOI: 10.4236/jct.2014.511106    2,390 Downloads   2,957 Views  

ABSTRACT

he frequency of EGFR mutations is ethnicity-dependent, with a higher proportion in Asian population than in whites. The prevalence of these mutations among Arab patients is unknown. The objective of this study was to report the frequency and spectrum of EGFR mutations in our population with lung adenocarcinoma, and the effect of this mutation on treatment outcome. Tumor specimens from 81 patients histological diagnosed as NSCLC adenocarcinoma were reviewed by our local pathologist and then sent to Lab 21 London, UK. Samples were tested for 28 mutations in EGFR gene. Positive patients received TKI and negative patients received chemotherapy. Data were collected and retrospectively analyzed to determine frequency and spectrum of EGFR positivity. Patients were followed for time to progression (TTP) and overall survival (OS). Overall frequency of EGFR mutation was 37%; Del 19 (46.6%), L858R (40%), D719x and insertion 20 (6.7%) for each. Females and nonsmokers exhibited a statistically significant higher EGFR positivity (P = 0.003, 0.059) respectively. Overall response rate (ORR) was 76.6% and 43% in EGFR positive and negative cases respectively (P = 0.002). There was a statistically significant difference in TTP and OS between EGFR positive and negative patients (P = 0.035 and 0.039 respectively). Arab patients exhibit an EGFR mutation pattern that is closer to Asian population. EGFR gene mutation subtypes are the same as that reported worldwide. A statistically significant TTP and OS benefit was noticed in EGFR positive patients compared to EGFR negative cases.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Shafik, H. , Al-Shemarri, S. , Al-Enezi, F. , Ashour, M. , Khalaf, E. and Al-Khodary, A. (2014) Frequency of Epidermal Growth Factor Mutation Status and Its Effect on Outcome of Patients with Adenocarcinoma of the Lung. Journal of Cancer Therapy, 5, 1012-1020. doi: 10.4236/jct.2014.511106.

References

[1] Elbasmi, A., Al-Asfour, A., Al-Nesf, Y. and Al-Awadi, A. (2010) Cancer in Kuwait Magnitude of the Problem. GJO, 8, 7-14.
[2] Azzoli, C.G., Baker, S.J., Temin, S., et al. (2009) American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 27, 6251-6266. http://dx.doi.org/10.1200/JCO.2009.23.5622
[3] Shigematsu, H., Lin, L., Takahashi, T., et al. (2005) Clinical and Biological Features Associated with Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers. Journal of the National Cancer Institute, 97, 339-346. http://dx.doi.org/10.1093/jnci/dji055
[4] Shi, Y., Au, J.S., Thongprasert, S., et al. (2014) A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non-Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER). Journal of Thoracic Oncology, 9, 154-162.
http://dx.doi.org/10.1097/JTO.0000000000000033
[5] Reily, G.J., Politi, K.A., Miller, V.A. and Pao, W. (2006) Update on Epidermal Growth Factor Receptor Mutation in NSCLC. Clinical Cancer Research, 12, 7232-7241. http://dx.doi.org/10.1158/1078-0432.CCR-06-0658
[6] Pao, W., Miller, V., Zakowski, M., et al. (2004) EGF Receptor Gene Mutations Are Common in Lung Cancers from “Never Smokers” and Are Associated with Sensitivity of Tumors to Gefitinib and Erlotinib. The Proceedings of the National Academy of Sciences of the United States of America, 101, 13306-13311. http://dx.doi.org/10.1073/pnas.0405220101
[7] Miller, V.A., Riely, G.J., Zakowski, M.F., et al. (2008) Molecular Characteristics of Broncho-Alvealar and Adenocarcinoma, Broncho-Alveolar Carcinoma Subtype, Predict Response to Erlotinib. Journal of Clinical Oncology, 26, 1472-1478. http://dx.doi.org/10.1200/JCO.2007.13.0062
[8] Lee, C.K., Brown, C., Gralla, R.J., et al. (2013) Impact of EGFR Inhibitor in Non-Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis. Journal of the National Cancer Institute, 105, 595-605. http://dx.doi.org/10.1093/jnci/djt072
[9] Fukuoka, M., Wu, Y.L., Thongprasert, S., et al. (2011) Biomarker Analyses and Final Overall Survival Results from a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib versus Carboplatin/Paclitaxel in Clinically Selected Patients with Advanced Non-Small-Cell Lung Cancer in Asia (IPASS). Journal of Clinical Oncology, 29, 2866-2874.
http://dx.doi.org/10.1200/JCO.2010.33.4235
[10] Inoue, A., Kobayashi, K., Maemondo, M., et al. (2013) Updated Overall Survival Results from a Randomized Phase III Trial Comparing Gefitinib with Carboplatin-Paclitaxel for Chemo-Na?ve Non-Small Cell Lung Cancer with Sensitive EGFR Gene Mutations (NEJ002). Annals of Oncology, 24, 54-59. http://dx.doi.org/10.1093/annonc/mds214
[11] Maemondo, M., Inoue, A., Kobayashi, K., et al. (2010) Gefitinib or Chemotherapy for Non-Small-Cell Lung Cancer with Mutated EGFR. The New England Journal of Medicine, 362, 2380-2388. http://dx.doi.org/10.1056/NEJMoa0909530
[12] Mitsudomi, T., Morita, S., Yatabe, Y., et al. (2010) Gefitinib versus Cisplatin plus Docetaxel in Patients with Non-Small-Cell Lung Cancer Harboring Mutations of the Epidermal Growth Factor Receptor (WJTOG3405): An Open Label, Randomised Phase 3 Trial. The Lancet Oncology, 11, 121-128. http://dx.doi.org/10.1016/S1470-2045(09)70364-X
[13] Zhou, C., Wu, Y.L., Chen, G., et al. (2011) Erlotinib versus Chemotherapy as First-Line Treatment for Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer (OPTIMAL, CTONG-0802): A Multicentre, Open Label, Randomised, Phase 3 Study. The Lancet Oncology, 12, 735-742. http://dx.doi.org/10.1016/S1470-2045(11)70184-X
[14] Rosell, R., Carcereny, E., Gervais, R., et al. (2012) Erlotinib versus Standard Chemotherapy as First-Line Treatment for European Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer (EURTAC): A Multicentre, Open-Label, Randomised Phase 3 Trial. The Lancet Oncology, 13, 239-246. http://dx.doi.org/10.1016/S1470-2045(11)70393-X
[15] Sharma, S.V., Bell, D.W., Settleman, J. and Haber, D.A. (2007) Epidermal Growth Factor Mutation in Lung Cancer. Nature Reviews Cancer, 7, 169-181. http://dx.doi.org/10.1038/nrc2088
[16] Johnson, B., et al. (2013) A Multicenter Effort to Identify Driver Mutations and Employ Targeted Therapy in Patients with Lung Adenocarcinomas: The Lung Cancer Mutation Consortium. JCO, 31, Abstract 8019.
[17] Ardizzoni, A., Boni, L., Tiseo, M., et al. (2007) Cisplatin versus Carboplatin-Based Chemotherapy in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: An Individual Patient Data Meta-Analysis. Journal of the National Cancer Institute, 99, 847-857. http://dx.doi.org/10.1093/jnci/djk196
[18] Scagliotti, G.V., Parikh, P., von Pawel, J., et al. (2008) Phase III Study Comparing Cisplatin plus Gemcitabine with Cisplatin plus Pemetrexed in Chemotherapy-Naive Patients with Advanced-Stage Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 26, 3543-3551.
http://dx.doi.org/10.1200/JCO.2007.15.0375
[19] Syrigos, K.N., Vansteenkiste, J., Parikh, P., von Pawel, J., Manegold, C., Martins, R.G., et al. (2010) Prognostic and Predictive Factors in a Randomized Phase III Trial Comparing Cisplatin-Pemetrexed versus Cisplatin-Gemcitabine in Advanced Non-Small-Cell Lung Cancer. Annals of Oncology, 21, 556-561. http://dx.doi.org/10.1093/annonc/mdp392

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.