BACKGROUND: Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes, including epidermal growth factor receptor (EGFR) and KRAS. Mutations in EGFR are associated with both improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. For the current report, the authors examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. METHODS: Data were analyzed from patients with advanced lung adenocarcinomas who had known EGFR and KRAS mutation status evaluated between 2002 and 2009. The collected clinical variables included age, sex, Karnofsky performance status, smoking history, and treatment history. Overall survival from the diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: In total, 1036 patients were evaluated, including 610 women (59%) and 344 never-smokers (33%). The median patient age was 65 years (range, 25-92 years), and the majority of patients (81%) had a Karnofsky performance status ≥80%. In multivariate analysis, EGFR mutations were associated with longer overall survival (hazard ratio, 0.6; P < .001), and KRAS mutations were associated with shorter survival (hazard ratio, 1.21; P = .048). CONCLUSIONS: KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas and should be determined in patients when they are diagnosed with advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors.
BACKGROUND:Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes, including epidermal growth factor receptor (EGFR) and KRAS. Mutations in EGFR are associated with both improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. For the current report, the authors examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. METHODS: Data were analyzed from patients with advanced lung adenocarcinomas who had known EGFR and KRAS mutation status evaluated between 2002 and 2009. The collected clinical variables included age, sex, Karnofsky performance status, smoking history, and treatment history. Overall survival from the diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: In total, 1036 patients were evaluated, including 610 women (59%) and 344 never-smokers (33%). The median patient age was 65 years (range, 25-92 years), and the majority of patients (81%) had a Karnofsky performance status ≥80%. In multivariate analysis, EGFR mutations were associated with longer overall survival (hazard ratio, 0.6; P < .001), and KRAS mutations were associated with shorter survival (hazard ratio, 1.21; P = .048). CONCLUSIONS:KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas and should be determined in patients when they are diagnosed with advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors.
Authors: R J Slebos; R E Kibbelaar; O Dalesio; A Kooistra; J Stam; C J Meijer; S S Wagenaar; R G Vanderschueren; N van Zandwijk; W J Mooi Journal: N Engl J Med Date: 1990-08-30 Impact factor: 91.245
Authors: J P O'Connell; M G Kris; R J Gralla; S Groshen; A Trust; J J Fiore; D P Kelsen; R T Heelan; R B Golbey Journal: J Clin Oncol Date: 1986-11 Impact factor: 44.544
Authors: William Pao; Vincent Miller; Maureen Zakowski; Jennifer Doherty; Katerina Politi; Inderpal Sarkaria; Bhuvanesh Singh; Robert Heelan; Valerie Rusch; Lucinda Fulton; Elaine Mardis; Doris Kupfer; Richard Wilson; Mark Kris; Harold Varmus Journal: Proc Natl Acad Sci U S A Date: 2004-08-25 Impact factor: 11.205
Authors: J Guillermo Paez; Pasi A Jänne; Jeffrey C Lee; Sean Tracy; Heidi Greulich; Stacey Gabriel; Paula Herman; Frederic J Kaye; Neal Lindeman; Titus J Boggon; Katsuhiko Naoki; Hidefumi Sasaki; Yoshitaka Fujii; Michael J Eck; William R Sellers; Bruce E Johnson; Matthew Meyerson Journal: Science Date: 2004-04-29 Impact factor: 47.728
Authors: Thomas J Lynch; Daphne W Bell; Raffaella Sordella; Sarada Gurubhagavatula; Ross A Okimoto; Brian W Brannigan; Patricia L Harris; Sara M Haserlat; Jeffrey G Supko; Frank G Haluska; David N Louis; David C Christiani; Jeff Settleman; Daniel A Haber Journal: N Engl J Med Date: 2004-04-29 Impact factor: 91.245
Authors: S G Spiro; R M Rudd; R L Souhami; J Brown; D J Fairlamb; N H Gower; L Maslove; R Milroy; V Napp; M K B Parmar; M D Peake; R J Stephens; H Thorpe; D A Waller; P West Journal: Thorax Date: 2004-10 Impact factor: 9.139
Authors: T Mitsudomi; S M Steinberg; H K Oie; J L Mulshine; R Phelps; J Viallet; H Pass; J D Minna; A F Gazdar Journal: Cancer Res Date: 1991-09-15 Impact factor: 12.701
Authors: M Paesmans; J P Sculier; P Libert; G Bureau; G Dabouis; J Thiriaux; J Michel; O Van Cutsem; R Sergysels; P Mommen Journal: J Clin Oncol Date: 1995-05 Impact factor: 44.544
Authors: C Mascaux; N Iannino; B Martin; M Paesmans; T Berghmans; M Dusart; A Haller; P Lothaire; A-P Meert; S Noel; J-J Lafitte; J-P Sculier Journal: Br J Cancer Date: 2005-01-17 Impact factor: 7.640
Authors: F Koinis; A Voutsina; A Kalikaki; A Koutsopoulos; E Lagoudaki; E Tsakalaki; E K Dermitzaki; E Kontopodis; A G Pallis; V Georgoulias; A Kotsakis Journal: Clin Transl Oncol Date: 2017-06-19 Impact factor: 3.405
Authors: Badi El Osta; Madhusmita Behera; Sungjin Kim; Lynne D Berry; Gabriel Sica; Rathi N Pillai; Taofeek K Owonikoko; Mark G Kris; Bruce E Johnson; David J Kwiatkowski; Lynette M Sholl; Dara L Aisner; Paul A Bunn; Fadlo R Khuri; Suresh S Ramalingam Journal: J Thorac Oncol Date: 2019-02-05 Impact factor: 15.609
Authors: Helena A Yu; Camelia S Sima; Matthew D Hellmann; Jarushka Naidoo; Natalie Busby; Katherine Rodriguez; Gregory J Riely; Mark G Kris Journal: Cancer Date: 2015-03-17 Impact factor: 6.860
Authors: Geoffrey R Oxnard; Peter C Lo; Mizuki Nishino; Suzanne E Dahlberg; Neal I Lindeman; Mohit Butaney; David M Jackman; Bruce E Johnson; Pasi A Jänne Journal: J Thorac Oncol Date: 2013-02 Impact factor: 15.609
Authors: Anna M Varghese; Camelia S Sima; Jamie E Chaft; Melissa L Johnson; Gregory J Riely; Marc Ladanyi; Mark G Kris Journal: J Thorac Oncol Date: 2013-01 Impact factor: 15.609
Authors: Etay Ziv; Joseph P Erinjeri; Hooman Yarmohammadi; F Edward Boas; Elena N Petre; Song Gao; Waleed Shady; Constantinos T Sofocleous; David R Jones; Charles M Rudin; Stephen B Solomon Journal: Radiology Date: 2016-07-19 Impact factor: 11.105