Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21
- PMID: 18626007
- DOI: 10.1200/JCO.2007.14.8924
Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21
Abstract
Purpose: To evaluate the effect of KRAS and epidermal growth factor receptor (EGFR) genotype on the response to erlotinib treatment in the BR.21, placebo-controlled trial.
Patients and methods: We analyzed 206 tumors for KRAS mutation, 204 tumors for EGFR mutation, and 159 tumors for EGFR gene copy by fluorescent in situ hybridization (FISH). We reanalyzed EGFR deletion/mutation using two highly sensitive techniques that detect abnormalities in samples with 5% to 10% tumor cellularity. KRAS mutation was analyzed by direct sequencing.
Results: Thirty patients (15%) had KRAS mutations, 34 (17%) had EGFR exon 19 deletion or exon 21 L858R mutations, and 61 (38%) had high EGFR gene copy (FISH positive). Response rates were 10% for wild-type and 5% for mutant KRAS (P = .69), 7% for wild-type and 27% for mutant EGFR (P = .03), and 5% for EGFR FISH-negative and 21% for FISH-positive patients (P = .02). Significant survival benefit from erlotinib therapy was observed for patients with wild-type KRAS (hazard ratio [HR] = 0.69, P = .03) and EGFR FISH positivity (HR = 0.43, P = .004) but not for patients with mutant KRAS (HR = 1.67, P = .31), wild-type EGFR (HR = 0.74, P = .09), mutant EGFR (HR = 0.55, P = .12), and EGFR FISH negativity (HR = 0.80, P = .35). In multivariate analysis, only EGFR FISH-positive status was prognostic for poorer survival (P = .025) and predictive of differential survival benefit from erlotinib (P = .005).
Conclusion: EGFR mutations and high copy number are predictive of response to erlotinib. EGFR FISH is the strongest prognostic marker and a significant predictive marker of differential survival benefit from erlotinib.
Similar articles
-
Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer.J Clin Oncol. 2011 Nov 1;29(31):4113-20. doi: 10.1200/JCO.2010.31.8162. Epub 2011 Oct 3. J Clin Oncol. 2011. PMID: 21969500 Clinical Trial.
-
Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study.J Thorac Oncol. 2008 Dec;3(12):1446-53. doi: 10.1097/JTO.0b013e31818ddcaa. J Thorac Oncol. 2008. PMID: 19057271 Clinical Trial.
-
Impact of systematic EGFR and KRAS mutation evaluation on progression-free survival and overall survival in patients with advanced non-small-cell lung cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part 2).J Thorac Oncol. 2012 Oct;7(10):1490-502. doi: 10.1097/JTO.0b013e318265b2b5. J Thorac Oncol. 2012. PMID: 22982650
-
Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?J Clin Oncol. 2010 Nov 1;28(31):4769-77. doi: 10.1200/JCO.2009.27.4365. Epub 2010 Oct 4. J Clin Oncol. 2010. PMID: 20921461 Review.
-
KRAS mutations as prognostic and predictive markers in non-small cell lung cancer.J Thorac Oncol. 2013 May;8(5):530-42. doi: 10.1097/JTO.0b013e318283d958. J Thorac Oncol. 2013. PMID: 23524403 Review.
Cited by
-
The association of EGFR amplification with aberrant exon 20 insertion report using the cobas EGFR Mutation Test v2.PLoS One. 2024 Apr 30;19(4):e0301120. doi: 10.1371/journal.pone.0301120. eCollection 2024. PLoS One. 2024. PMID: 38687753 Free PMC article.
-
KRAS G12 isoforms exert influence over up-front treatments: A retrospective, multicenter, Italian analysis of the impact of first-line immune checkpoint inhibitors in an NSCLC real-life population.Front Oncol. 2022 Nov 14;12:968064. doi: 10.3389/fonc.2022.968064. eCollection 2022. Front Oncol. 2022. PMID: 36452502 Free PMC article.
-
Prognostic Impact of EGFR Amplification and Visceral Pleural Invasion in Early Stage Pulmonary Squamous Cell Carcinomas Patients after Surgical Resection of Primary Tumor.Cancers (Basel). 2022 Apr 27;14(9):2174. doi: 10.3390/cancers14092174. Cancers (Basel). 2022. PMID: 35565304 Free PMC article.
-
FOCUS4 biomarker laboratories: from the benefits to the practical and logistical issues faced during 6 years of centralised testing.J Clin Pathol. 2023 Aug;76(8):548-554. doi: 10.1136/jclinpath-2022-208233. Epub 2022 Mar 7. J Clin Pathol. 2023. PMID: 35256486 Free PMC article.
-
Age Effects Aggressive Behavior: RNA-Seq Analysis in Cattle with Implications for Studying Neoteny Under Domestication.Behav Genet. 2022 Mar;52(2):141-153. doi: 10.1007/s10519-021-10097-1. Epub 2022 Jan 15. Behav Genet. 2022. PMID: 35032285 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous