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出境医 / 临床实验 / K-RAS and EGFR in Lung Cancer (K-RAS_NSCLC)

K-RAS and EGFR in Lung Cancer (K-RAS_NSCLC)

Study Description
Brief Summary:
Retrospective analysis where patients with histologically confirmed Non-small cell lung cancer (NSCLC) were centrally evaluated for the presence of KRAS and EGFR mutations.

Condition or disease
Non Small Cell Lung Cancer

Detailed Description:
A retrospective analysis, performed by the Hellenic Co-operative Oncology Group (HeCOG), in samples from patients with histologically confirmed NSCLC, who had been treated within HeCOG-affiliated centres from March 2000 through December 2012, were centrally evaluated for the presence of KRAS and EGFR mutations. All patients had available clinicopathological data at diagnosis. Formalin-fixed, paraffin-embedded tissue blocks were retrospectively retrieved from the HeCOG tumor repository. Cytologic material was prospectively submitted for genotyping in more recent years (2010-2012).
Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 424 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Genotyping K-RAS and EGFR in Greek Non-small-cell Lung Cancer Patients: Incidence, Significance and Treatment Implications
Actual Study Start Date : March 2000
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2014
Arms and Interventions
Group/Cohort
K-RAS and EGFR mutated
Wild type
Outcome Measures
Primary Outcome Measures :
  1. Progression free survival [ Time Frame: from the date of treatment start until verified disease progression, death from any cause or date of last contact whichever occurred first, up to 9 months ]
  2. Overall survival [ Time Frame: from the date of treatment start until verified disease progression, death from any cause or date of last contact whichever occurred first, up to 36 months ]

Biospecimen Retention:   Samples With DNA
Formalin- fixed paraffin- embedded tissue blocks.

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients treated within HeCOG-affiliated centres from March 2000 through December 2012.
Criteria

Inclusion Criteria:

  • Patients with histologically confirmed NSCLC
  • Signed and dated written informed consent
  • Age 18 years
  • Available cytological material

Exclusion Criteria: -

Contacts and Locations

Locations
Layout table for location information
Greece
Oncology Unit, Metropolitan Hospital
Néo Fáliro, Athens, Greece, 18547
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
Tracking Information
First Submitted Date May 10, 2019
First Posted Date May 15, 2019
Last Update Posted Date May 15, 2019
Actual Study Start Date March 2000
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 14, 2019)
  • Progression free survival [ Time Frame: from the date of treatment start until verified disease progression, death from any cause or date of last contact whichever occurred first, up to 9 months ]
  • Overall survival [ Time Frame: from the date of treatment start until verified disease progression, death from any cause or date of last contact whichever occurred first, up to 36 months ]
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title K-RAS and EGFR in Lung Cancer
Official Title Genotyping K-RAS and EGFR in Greek Non-small-cell Lung Cancer Patients: Incidence, Significance and Treatment Implications
Brief Summary Retrospective analysis where patients with histologically confirmed Non-small cell lung cancer (NSCLC) were centrally evaluated for the presence of KRAS and EGFR mutations.
Detailed Description A retrospective analysis, performed by the Hellenic Co-operative Oncology Group (HeCOG), in samples from patients with histologically confirmed NSCLC, who had been treated within HeCOG-affiliated centres from March 2000 through December 2012, were centrally evaluated for the presence of KRAS and EGFR mutations. All patients had available clinicopathological data at diagnosis. Formalin-fixed, paraffin-embedded tissue blocks were retrospectively retrieved from the HeCOG tumor repository. Cytologic material was prospectively submitted for genotyping in more recent years (2010-2012).
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Formalin- fixed paraffin- embedded tissue blocks.
Sampling Method Non-Probability Sample
Study Population Patients treated within HeCOG-affiliated centres from March 2000 through December 2012.
Condition Non Small Cell Lung Cancer
Intervention Not Provided
Study Groups/Cohorts
  • K-RAS and EGFR mutated
  • Wild type
Publications *
  • Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. Epub 2004 Apr 29.
  • Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007 Aug 2;448(7153):561-6. Epub 2007 Jul 11.
  • Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FR. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23. Review.
  • Shepherd FA, Tsao MS. Unraveling the mystery of prognostic and predictive factors in epidermal growth factor receptor therapy. J Clin Oncol. 2006 Mar 1;24(7):1219-20; author reply 1220-1.
  • Zhang Z, Wang T, Zhang J, Cai X, Pan C, Long Y, Chen J, Zhou C, Yin X. Prognostic value of epidermal growth factor receptor mutations in resected non-small cell lung cancer: a systematic review with meta-analysis. PLoS One. 2014 Aug 27;9(8):e106053. doi: 10.1371/journal.pone.0106053. eCollection 2014. Review.
  • Pesek M, Benesova L, Belsanova B, Mukensnabl P, Bruha F, Minarik M. Dominance of EGFR and insignificant KRAS mutations in prediction of tyrosine-kinase therapy for NSCLC patients stratified by tumor subtype and smoking status. Anticancer Res. 2009 Jul;29(7):2767-73.
  • Satoh T, Nakafuku M, Kaziro Y. Function of Ras as a molecular switch in signal transduction. J Biol Chem. 1992 Dec 5;267(34):24149-52. Review.
  • Wood K, Hensing T, Malik R, Salgia R. Prognostic and Predictive Value in KRAS in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016 Jun 1;2(6):805-12. doi: 10.1001/jamaoncol.2016.0405. Review.
  • Garassino MC, Marabese M, Rusconi P, Rulli E, Martelli O, Farina G, Scanni A, Broggini M. Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann Oncol. 2011 Jan;22(1):235-237. doi: 10.1093/annonc/mdq680.
  • Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, Tsao A, Liu S, Larsen JE, Wang J, Diao L, Coombes KR, Chen L, Zhang S, Abdelmelek MF, Tang X, Papadimitrakopoulou V, Minna JD, Lippman SM, Hong WK, Herbst RS, Wistuba II, Heymach JV, Powis G. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. J Natl Cancer Inst. 2012 Feb 8;104(3):228-39. doi: 10.1093/jnci/djr523. Epub 2012 Jan 13.
  • Lee T, Lee B, Choi YL, Han J, Ahn MJ, Um SW. Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases. J Pathol Transl Med. 2016 May;50(3):197-203. doi: 10.4132/jptm.2016.03.09. Epub 2016 Apr 18.
  • Lee B, Lee T, Lee SH, Choi YL, Han J. Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers. Oncotarget. 2016 Apr 26;7(17):23874-84. doi: 10.18632/oncotarget.8074.
  • Riely GJ, Kris MG, Rosenbaum D, Marks J, Li A, Chitale DA, Nafa K, Riedel ER, Hsu M, Pao W, Miller VA, Ladanyi M. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 2008 Sep 15;14(18):5731-4. doi: 10.1158/1078-0432.CCR-08-0646.
  • Shepherd FA, Domerg C, Hainaut P, Jänne PA, Pignon JP, Graziano S, Douillard JY, Brambilla E, Le Chevalier T, Seymour L, Bourredjem A, Le Teuff G, Pirker R, Filipits M, Rosell R, Kratzke R, Bandarchi B, Ma X, Capelletti M, Soria JC, Tsao MS. Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol. 2013 Jun 10;31(17):2173-81. doi: 10.1200/JCO.2012.48.1390. Epub 2013 Apr 29.
  • Steuer CE, Behera M, Berry L, Kim S, Rossi M, Sica G, Owonikoko TK, Johnson BE, Kris MG, Bunn PA, Khuri FR, Garon EB, Ramalingam SS. Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium. Cancer. 2016 Mar 1;122(5):766-72. doi: 10.1002/cncr.29812. Epub 2015 Dec 22.
  • Kotoula V, Charalambous E, Biesmans B, Malousi A, Vrettou E, Fountzilas G, Karkavelas G. Targeted KRAS mutation assessment on patient tumor histologic material in real time diagnostics. PLoS One. 2009 Nov 4;4(11):e7746. doi: 10.1371/journal.pone.0007746.
  • Altman DG, McShane LM, Sauerbrei W, Taube SE. Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): explanation and elaboration. PLoS Med. 2012;9(5):e1001216. doi: 10.1371/journal.pmed.1001216. Epub 2012 May 29.
  • Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29;7(48):78985-78993. doi: 10.18632/oncotarget.12587. Review.
  • Barlesi F, Mazieres J, Merlio JP, Debieuvre D, Mosser J, Lena H, Ouafik L, Besse B, Rouquette I, Westeel V, Escande F, Monnet I, Lemoine A, Veillon R, Blons H, Audigier-Valette C, Bringuier PP, Lamy R, Beau-Faller M, Pujol JL, Sabourin JC, Penault-Llorca F, Denis MG, Lantuejoul S, Morin F, Tran Q, Missy P, Langlais A, Milleron B, Cadranel J, Soria JC, Zalcman G; Biomarkers France contributors. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016 Apr 2;387(10026):1415-1426. doi: 10.1016/S0140-6736(16)00004-0. Epub 2016 Jan 15.
  • Szumera-Ciećkiewicz A, Olszewski WT, Tysarowski A, Kowalski DM, Głogowski M, Krzakowski M, Siedlecki JA, Wągrodzki M, Prochorec-Sobieszek M. EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence. Int J Clin Exp Pathol. 2013 Nov 15;6(12):2800-12. eCollection 2013. Review.
  • Papadopoulou E, Tsoulos N, Tsirigoti A, Apessos A, Agiannitopoulos K, Metaxa-Mariatou V, Zarogoulidis K, Zarogoulidis P, Kasarakis D, Kakolyris S, Dahabreh J, Vlastos F, Zoublios C, Rapti A, Papageorgiou NG, Veldekis D, Gaga M, Aravantinos G, Karavasilis V, Karagiannidis N, Nasioulas G. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients. Oncol Lett. 2015 Oct;10(4):2176-2184. Epub 2015 Aug 12.
  • Mountzios G, Linardou H, S. A, editors. Epidemiology and incidence of EGFR mutation in Greek patients with advanced NSCLC. National Hellenic Oncology Meeting; 2016.
  • Linardou H, Dahabreh IJ, Bafaloukos D, Kosmidis P, Murray S. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol. 2009 Jun;6(6):352-66. doi: 10.1038/nrclinonc.2009.62. Review.
  • Murray S, Timotheadou E, Linardou H, Vrettou AV, Kostopoulos I, Skrickova J, Papakostantinou C, Christodoulou C, Pectasides D, Samantas E, Papakostas P, Skarlos DV, Kosmidis P, Fountzilas G. Mutations of the epidermal growth factor receptor tyrosine kinase domain and associations with clinicopathological features in non-small cell lung cancer patients. Lung Cancer. 2006 May;52(2):225-33. Epub 2006 Mar 29.
  • Linardou H, Briasoulis E, Dahabreh IJ, Mountzios G, Papadimitriou C, Papadopoulos S, Bafaloukos D, Kosmidis P, Murray S. All about KRAS for clinical oncology practice: gene profile, clinical implications and laboratory recommendations for somatic mutational testing in colorectal cancer. Cancer Treat Rev. 2011 May;37(3):221-33. doi: 10.1016/j.ctrv.2010.07.008. Epub 2010 Sep 29. Review.
  • Jung KJ, Jeon C, Jee SH. The effect of smoking on lung cancer: ethnic differences and the smoking paradox. Epidemiol Health. 2016 Dec 20;38:e2016060. doi: 10.4178/epih.e2016060. eCollection 2016. Review.
  • Rulli E, Marabese M, Torri V, Farina G, Veronese S, Bettini A, Longo F, Moscetti L, Ganzinelli M, Lauricella C, Copreni E, Labianca R, Martelli O, Marsoni S, Broggini M, Garassino MC; TAILOR trialists. Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial. Ann Oncol. 2015 Oct;26(10):2079-84. doi: 10.1093/annonc/mdv318. Epub 2015 Jul 24.
  • Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, Dusart M, Haller A, Lothaire P, Meert AP, Noel S, Lafitte JJ, Sculier JP. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer. 2005 Jan 17;92(1):131-9. Review.
  • Sun JM, Hwang DW, Ahn JS, Ahn MJ, Park K. Prognostic and predictive value of KRAS mutations in advanced non-small cell lung cancer. PLoS One. 2013 May 28;8(5):e64816. doi: 10.1371/journal.pone.0064816. Print 2013.
  • Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008 Oct;9(10):962-72. doi: 10.1016/S1470-2045(08)70206-7. Epub 2008 Sep 17. Review.
  • Svaton M, Fiala O, Pesek M, Bortlicek Z, Minarik M, Benesova L, Topolcan O. The Prognostic Role of KRAS Mutation in Patients with Advanced NSCLC Treated with Second- or Third-line Chemotherapy. Anticancer Res. 2016 Mar;36(3):1077-82.
  • Bonanno L, Schiavon M, Nardo G, Bertorelle R, Bonaldi L, Galligioni A, Indraccolo S, Pasello G, Rea F, Favaretto A. Prognostic and predictive implications of EGFR mutations, EGFR copy number and KRAS mutations in advanced stage lung adenocarcinoma. Anticancer Res. 2010 Dec;30(12):5121-8.
  • Fan G, Zhang K, Ding J, Li J. Prognostic value of EGFR and KRAS in circulating tumor DNA in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2017 May 16;8(20):33922-33932. doi: 10.18632/oncotarget.15412. Review.
  • Shen H, Che K, Cong L, Dong W, Zhang T, Liu Q, Du J. Diagnostic and prognostic value of blood samples for KRAS mutation identification in lung cancer: a meta-analysis. Oncotarget. 2017 May 30;8(22):36812-36823. doi: 10.18632/oncotarget.15972. Review.
  • Lohinai Z, Klikovits T, Moldvay J, Ostoros G, Raso E, Timar J, Fabian K, Kovalszky I, Kenessey I, Aigner C, Renyi-Vamos F, Klepetko W, Dome B, Hegedus B. KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis. Sci Rep. 2017 Jan 4;7:39721. doi: 10.1038/srep39721.
  • Zhao N, Wilkerson MD, Shah U, Yin X, Wang A, Hayward MC, Roberts P, Lee CB, Parsons AM, Thorne LB, Haithcock BE, Grilley-Olson JE, Stinchcombe TE, Funkhouser WK, Wong KK, Sharpless NE, Hayes DN. Alterations of LKB1 and KRAS and risk of brain metastasis: comprehensive characterization by mutation analysis, copy number, and gene expression in non-small-cell lung carcinoma. Lung Cancer. 2014 Nov;86(2):255-61. doi: 10.1016/j.lungcan.2014.08.013. Epub 2014 Aug 30.
  • Mellema WW, Dingemans AM, Thunnissen E, Snijders PJ, Derks J, Heideman DA, Van Suylen R, Smit EF. KRAS mutations in advanced nonsquamous non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy have no predictive value. J Thorac Oncol. 2013 Sep;8(9):1190-5. doi: 10.1097/JTO.0b013e318298764e.
  • Dong X, Zhao X, Hao Y, Wei Y, Yin Q, Du J. Response to first-line chemotherapy in patients with non-small-cell lung cancer according to epidermal growth factor receptor and K-RAS mutation status. Clin Lung Cancer. 2013 Nov;14(6):680-7. doi: 10.1016/j.cllc.2013.05.004. Epub 2013 Jul 31.
  • Marabese M, Ganzinelli M, Garassino MC, Shepherd FA, Piva S, Caiola E, Macerelli M, Bettini A, Lauricella C, Floriani I, Farina G, Longo F, Bonomi L, Fabbri MA, Veronese S, Marsoni S, Broggini M, Rulli E. KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy. Oncotarget. 2015 Oct 20;6(32):34014-22. doi: 10.18632/oncotarget.5607.
  • Zhang Y, Fang W, Yan Y, Wang M, Kang S, Sheng J, Zhan J, Chen N, Hong S, Yang Y, Ma Y, He D, Qin T, Zhou T, Tang Y, He X, Liang W, Zhang L. The efficacy of first-line chemotherapy is associated with KRAS mutation status in patients with advanced non-small cell lung cancer: a meta-analysis. Med Oncol. 2015 Mar;32(3):61. doi: 10.1007/s12032-015-0489-y. Epub 2015 Feb 8.
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  • Arrieta O, Cardona AF, Corrales L, Campos-Parra AD, Sánchez-Reyes R, Amieva-Rivera E, Rodríguez J, Vargas C, Carranza H, Otero J, Karachaliou N, Astudillo H, Rosell R; CLICaP. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer. Lung Cancer. 2015 Feb;87(2):169-75. doi: 10.1016/j.lungcan.2014.12.009. Epub 2014 Dec 18.
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: May 14, 2019) 		424
Original Actual Enrollment Same as current
Actual Study Completion Date December 2014
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients with histologically confirmed NSCLC
  • Signed and dated written informed consent
  • Age 18 years
  • Available cytological material

Exclusion Criteria: -
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Greece
Removed Location Countries  
 
Administrative Information
NCT Number NCT03951233
Other Study ID Numbers K-RAS_NSCLC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Hellenic Cooperative Oncology Group
Study Sponsor Hellenic Cooperative Oncology Group
Collaborators Not Provided
Investigators Not Provided
PRS Account Hellenic Cooperative Oncology Group
Verification Date May 2019

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