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Rennert G, Gottfried M, Rennert HS, et al. Long term follow-up of EGFR mutated NSCLC cases. Transl Oncol. 2020;14(1):100934doi: 10.1016/j.tranon.2020.100934.
Rennert, G., Gottfried, M., Rennert, H. S., Lejbkowicz, F., Frank, M., Cohen, I., Kelt, S., Agbarya, A., Dudnik, E., Dudnik, J., Katznelson, R., Mishali, M., Maimon Rabinovich, N., Nechushtan, H., Onn, A., Keren Rosenberg, S., Wollner, M., Zer, A., Bar, J., & Gronich, N. (2021). Long term follow-up of EGFR mutated NSCLC cases. Translational oncology, 14(1), 100934. https://doi.org/10.1016/j.tranon.2020.100934
Rennert, Gad, et al. "Long term follow-up of EGFR mutated NSCLC cases." Translational oncology vol. 14,1 (2021): 100934. doi: https://doi.org/10.1016/j.tranon.2020.100934
Rennert G, Gottfried M, Rennert HS, Lejbkowicz F, Frank M, Cohen I, Kelt S, Agbarya A, Dudnik E, Dudnik J, Katznelson R, Mishali M, Maimon Rabinovich N, Nechushtan H, Onn A, Keren Rosenberg S, Wollner M, Zer A, Bar J, Gronich N. Long term follow-up of EGFR mutated NSCLC cases. Transl Oncol. 2021 Jan;14(1):100934. doi: 10.1016/j.tranon.2020.100934. Epub 2020 Nov 10. PMID: 33186889; PMCID: PMC7658494.
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Transl Oncol. 2021 Jan;14(1):100934. doi: 10.1016/j.tranon.2020.100934. Epub 2020 Nov 10.

Long term follow-up of EGFR mutated NSCLC cases.

Translational oncology

Gad Rennert, Maya Gottfried, Hedy S Rennert, Flavio Lejbkowicz, Meira Frank, Ilana Cohen, Shiri Kelt, Abed Agbarya, Elizabeta Dudnik, Julia Dudnik, Rivka Katznelson, Moshe Mishali, Natalie Maimon Rabinovich, Hovav Nechushtan, Amir Onn, Shoshana Keren Rosenberg, Mariana Wollner, Alona Zer, Jair Bar, Naomi Gronich

Affiliations

  1. Clalit Health Services National Cancer Control Center and Personalized Medicine Program, Israel; Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Office of Chief Physician, Clalit Health Services Headquarters, Tel Aviv, Israel. Electronic address: [email protected].
  2. Lung Cancer Unit, Meir Medical Center, 4428164 Kfar Saba, Israel.
  3. Clalit Health Services National Cancer Control Center and Personalized Medicine Program, Israel; Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  4. Oncology Unit, Bene Zion Medical Center, Haifa, Israel.
  5. Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
  6. Department of Oncology, Soroka University Medical Center (SUMC) and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
  7. Institute of Oncology, Kaplan Medical Center, Rehovot, Israel; Faculty of Medicine, Hebrew University, Jerusalem, Israel.
  8. Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
  9. Institute of Pulmonology, Sheba Medical Center, Tel Hashomer, Israel.
  10. Oncology Institute, Lin Medical Center and Carmel Medical Center, Haifa, Israel.
  11. Department of Oncology, Rambam Health Care Campus, Haifa, Israel.
  12. Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel.

PMID: 33186889 PMCID: PMC7658494 DOI: 10.1016/j.tranon.2020.100934

Abstract

PURPOSE: A substantial fraction of all non-small cell lung cancers(NSCLC) carry a mutation in the EGFR gene for which an effective treatment with anti-tyrosine kinases(TKIs) is available. We studied the long term survival of these patients following the introduction of TKIs.

EXPERIMENTAL DESIGN: All consecutive cases of NSCLC newly diagnosed with advanced disease were referred for free tumor EGFR mutation testing at Clalit's national personalized medicine laboratory. Mutations and deletions in target codons 18-21 of EGFR were sought using RT-PCR and fragment analysis. Comprehensive EMRs were used to collect full data on treatments and clinical status.

RESULTS: A cohort of 3,062 advanced NSCLC cases, included 481(15.7%) somatic EGFR mutation carriers (17.5% of all adenocarcinomas, 26.7% of females with adenocarcinomas). TKIs treatment to EGFR mutation carriers was provided to 85% of all eligible. After a median follow up period of 15.9 months for EGFR mutated cases the hazard ratio for overall survival of EGFR-mutated NSCLC treated with TKIs was 0.55(0.49-0.63, p<0.0001) when compared with EGFR wild-type(WT) tumors under usual care. After adjusting for age, sex, ethnicity, smoking history and tumor histology, all of which had an independently significant effect on survival, the HR for TKI-treated, EGFR-mutated tumors, was 0.63 (0.55-0.71, p<0.0001). Treating EGFR-WT cases with TKIs yielded a high HR=1.32 (1.19-1.48).

CONCLUSIONS: TKIs given to EGFR mutated advanced NSCLC demonstrated a substantial survival benefit for at least five years. Squamous histology, smoking, male sex and Arab ethnicity were associated with higher NSCLC mortality hazard. Treating non-EGFR-mutated NSCLC with TKIs seems detrimental. Statement of Significance: • TKIs given to EGFR mutated advanced NSCLC demonstrated a substantial survival benefit for at least five years but not much longer. • Treating non-EGFR-mutated NSCLC with TKIs seems detrimental and should probably be avoided. • Squamous histology of non-small cell lung cancer, smoking history, male sex and Arab ethnicity were associated with altogether higher NSCLC mortality hazard.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Conflict of interest statement

Declaration of Competing Interest None of the authors has any conflict of interests to report.

References

  1. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):839-44 - PubMed
  2. Exp Hematol. 2017 Feb;46:9-20 - PubMed
  3. J Thorac Oncol. 2012 Oct;7(10):1490-502 - PubMed
  4. J Clin Oncol. 2013 Sep 20;31(27):3327-34 - PubMed
  5. N Engl J Med. 2009 Sep 3;361(10):958-67 - PubMed
  6. Lancet Oncol. 2012 Mar;13(3):239-46 - PubMed
  7. Sci Rep. 2020 Jul 2;10(1):10881 - PubMed
  8. N Engl J Med. 2009 Sep 3;361(10):947-57 - PubMed
  9. N Engl J Med. 2005 Jul 14;353(2):123-32 - PubMed
  10. Chest. 2006 Dec;130(6):1796-802 - PubMed
  11. Oncotarget. 2017 Oct 12;8(58):98384-98393 - PubMed
  12. Oncologist. 2015 Mar;20(3):307-15 - PubMed
  13. Jpn J Clin Oncol. 2016 May;46(5):462-7 - PubMed
  14. Lung Cancer. 2020 Nov;149:10-16 - PubMed
  15. N Engl J Med. 2010 Jun 24;362(25):2380-8 - PubMed
  16. Ann Oncol. 2017 Nov 1;28(11):2715-2724 - PubMed
  17. Lung Cancer. 2014 May;84(2):196-202 - PubMed
  18. J Clin Pharm Ther. 2015 Dec;40(6):661-71 - PubMed
  19. N Engl J Med. 2015 Apr 30;372(18):1689-99 - PubMed
  20. N Engl J Med. 2018 Jan 11;378(2):113-125 - PubMed
  21. J Natl Cancer Inst. 2013 May 1;105(9):595-605 - PubMed
  22. Proteomics Clin Appl. 2020 Sep;14(5):e1900144 - PubMed
  23. World J Surg Oncol. 2017 Oct 16;15(1):184 - PubMed
  24. PLoS One. 2015 Nov 23;10(11):e0143515 - PubMed
  25. J Thorac Oncol. 2016 Apr;11(4):556-65 - PubMed
  26. Ann Oncol. 2016 Feb;27(2):358-9 - PubMed
  27. Clin Lung Cancer. 2012 Mar;13(2):107-14 - PubMed
  28. Am J Cancer Res. 2015 Aug 15;5(9):2892-911 - PubMed
  29. Ann Oncol. 2018 Jan 1;29(1):200-208 - PubMed
  30. Science. 2004 Jun 4;304(5676):1497-500 - PubMed
  31. Leukemia. 2019 Jan;33(1):75-87 - PubMed
  32. J Clin Oncol. 2014 Jun 20;32(18):1902-8 - PubMed
  33. Sci Transl Med. 2011 Mar 23;3(75):75ra26 - PubMed
  34. Chest. 2010 Sep;138(3):500-9 - PubMed
  35. Eur Respir J. 2015 Jul;46(1):280-2 - PubMed
  36. Cancer Epidemiol. 2015 Jun;39(3):291-7 - PubMed
  37. Clin Lung Cancer. 2015 Mar;16(2):144-151.e1 - PubMed
  38. N Engl J Med. 2004 May 20;350(21):2129-39 - PubMed
  39. Sci Data. 2019 Apr 9;6(1):21 - PubMed
  40. CA Cancer J Clin. 2017 Jan;67(1):7-30 - PubMed
  41. Lancet Oncol. 2015 Feb;16(2):141-51 - PubMed

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