Sandra P D'Angelo1, Yelena Y Janjigian1, Nicholas Ahye1, Gregory J Riely1, Jamie E Chaft2, Camelia S Sima3, Ronglai Shen3, Junting Zheng3, Joseph Dycoco4, Mark G Kris1, Maureen F Zakowski5, Marc Ladanyi5, Valerie Rusch4, Christopher G Azzoli1. 1. Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York. 2. Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York. Electronic address: chaftj@mskcc.org. 3. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York. 4. Department of Surgery, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York. 5. Department of Pathology, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
Abstract
BACKGROUND: EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear. METHODS: At our institution, resection specimens from patients with stage I-III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded. RESULTS: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend toward improved OS. CONCLUSIONS: Patients with resected stage I-III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs.
BACKGROUND:EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear. METHODS: At our institution, resection specimens from patients with stage I-III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded. RESULTS: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend toward improved OS. CONCLUSIONS:Patients with resected stage I-III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs.
Authors: Brian C Gulack; Chi-Fu Jeffrey Yang; Paul J Speicher; James M Meza; Lin Gu; Xiaofei Wang; Thomas A D'Amico; Matthew G Hartwig; Mark F Berry Journal: Lung Cancer Date: 2015-10-14 Impact factor: 5.705
Authors: Mark G Kris; Bruce E Johnson; Lynne D Berry; David J Kwiatkowski; A John Iafrate; Ignacio I Wistuba; Marileila Varella-Garcia; Wilbur A Franklin; Samuel L Aronson; Pei-Fang Su; Yu Shyr; D Ross Camidge; Lecia V Sequist; Bonnie S Glisson; Fadlo R Khuri; Edward B Garon; William Pao; Charles Rudin; Joan Schiller; Eric B Haura; Mark Socinski; Keisuke Shirai; Heidi Chen; Giuseppe Giaccone; Marc Ladanyi; Kelly Kugler; John D Minna; Paul A Bunn Journal: JAMA Date: 2014-05-21 Impact factor: 56.272
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