K-RAS and EGFR in Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

— K-RAS_NSCLC  

Official title:

Genotyping K-RAS and EGFR in Greek Non-small-cell Lung Cancer Patients: Incidence, Significance and Treatment Implications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03951233
• Other study ID #: K-RAS_NSCLC
• Status: Completed
• Start date: March 2000
• Est. completion date: December 2014

Study information

• Verified date: May 2019
• Source: Hellenic Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 424
• Est. completion date: December 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with histologically confirmed NSCLC

• Signed and dated written informed consent

• Age 18 years

• Available cytological material

Exclusion Criteria: -

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Locations

Country	Name	City	State
Greece	Oncology Unit, Metropolitan Hospital	Néo Fáliro	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Hellenic Cooperative Oncology Group

Country where clinical trial is conducted

Greece, 

References & Publications (44)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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):235-7. doi: 10.1093/annonc/mdq680. — View Citation

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. — View Citation

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. — View Citation

Kim JH, Kim HS, Kim BJ. Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review. Oncotarget. 2017 Jul 18;8(29):48248-48252. doi: 10.18632/oncotarget.17594. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Mountzios G, Linardou H, S. A, editors. Epidemiology and incidence of EGFR mutation in Greek patients with advanced NSCLC. National Hellenic Oncology Meeting; 2016.

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Szumera-Cieckiewicz A, Olszewski WT, Tysarowski A, Kowalski DM, Glogowski M, Krzakowski M, Siedlecki JA, Wagrodzki 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. — View Citation

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. — View Citation

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, Geisinger K, Hirsch FR, Ishikawa Y, Kerr KM, Noguchi M, Pelosi G, Powell CA, Tsao MS, Wistuba I; WHO Panel. The 2015 World Health Organizati — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 44 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		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
Primary	Overall survival		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