Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)

Introduction: Previously, we reported the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations in nonsmall-cell lung cancer (NSCLC) patients in Latin America. The EGFR mutation frequency was found between Asian (40%) and Caucasian (15%) populations. Here, we report the updated distribution of NSCLC mutations. Methods: A total of 5738 samples from NSCLC patients from Argentina (1713), Mexico (1417), Colombia (1939), Peru (393), Panama (174), and Costa Rica (102) were genotyped for EGFR and KRAS. Results: The median patient age was 62.2 ± 12.3 years; 53.5% were women, 46.7% had a history of smoking, and 95.2% had adenocarcinoma histology. The frequency of EGFR mutations was 26.0% (95% confidence interval [CI], 24.9–27.1; Argentina, 14.4% [12.8–15.6]; México, 34.3% [31.9–36.7]; Colombia, 24.7% [22.8–26.6]; Peru, 51.1% [46.2–55.9]; Panamá, 27.3 [20.7–33.9]; and Costa Rica, 31.4% [22.4–40.4]). The frequency of KRAS mutations was 14.0% (9.1–18.9). In patients with adenocarcinoma, EGFR mutations were independently associated with gender (30.7% females vs. 18.4% males; p < 0.001), nonsmoker status (27.4% vs. 17.1%, p < 0.001), ethnicity (mestizo/indigenous, 35.3% vs. Caucasian, 13.7%, p < 0.001), and the absence of KRAS mutation (38.1% vs. 4.7%; p < 0.001). The overall response rate to EGFR tyrosine kinase inhibitors was 60.6% (95% CI, 52–69), with a median progression-free survival and overall survival of 15.9 (95% CI, 12.420.6) and 32 months (95% CI, 26.5–37.6), respectively. Conclusion: Our findings support the genetic heterogeneity of NSCLC in Latin America, confirming that the frequency of EGFR mutations is intermediate between that observed in the Asian and Caucasian populations.

[1]  A. Cardona,et al.  KRAS Mutation as the Biomarker of Response to Chemotherapy and EGFR-TKIs in Patients With Advanced Non–Small Cell Lung Cancer: Clues For Its Potential Use in Second-Line Therapy Decision Making , 2015, American journal of clinical oncology.

[2]  Jun Zhou,et al.  A comparison of epidermal growth factor receptor mutation testing methods in different tissue types in non-small cell lung cancer. , 2014, International journal of molecular medicine.

[3]  Shaozhang Zhou,et al.  Comparison of ARMS and direct sequencing for detection of EGFR mutation and prediction of EGFR-TKI efficacy between surgery and biopsy tumor tissues in NSCLC patients , 2014, Medical Oncology.

[4]  Wei Zhang,et al.  EGFR mutations in US Hispanic versus non-Hispanic white patients with lung adenocarcinoma. , 2014, Archives of pathology & laboratory medicine.

[5]  A. Gazdar EGFR mutations in lung cancer: different frequencies for different folks. , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  S. Thongprasert,et al.  A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER) , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[7]  T. Chou,et al.  Clinical Characteristics and Treatment Outcomes of Lung Adenocarcinomas with Discrepant EGFR Mutation Testing Results Derived from PCR-Direct Sequencing and Real-Time PCR-Based Assays , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[8]  A. Dutt,et al.  Frequency of EGFR Mutations in 907 Lung Adenocarcioma Patients of Indian Ethnicity , 2013, PloS one.

[9]  H. Wakelee,et al.  How do social factors explain outcomes in non-small-cell lung cancer among Hispanics in California? Explaining the Hispanic paradox. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  C. Liam,et al.  Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma in Malaysian Patients , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[11]  Richard Sullivan,et al.  Planning cancer control in Latin America and the Caribbean. , 2013, The Lancet. Oncology.

[12]  P. Pinheiro The influence of Hispanic ethnicity on nonsmall cell lung cancer histology and patient survival , 2013, Cancer.

[13]  R. Perez-Padilla,et al.  [National consensus of diagnosis and treatment of non-small cell lung cancer]. , 2013, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[14]  Abelardo Meneses-García,et al.  Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas , 2013 .

[15]  Y. Baskın,et al.  Relationship between epidermal growth factor receptor gene mutations and clinicopathological features in patients with non-small cell lung cancer in western Turkey. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[16]  Deepa Naishadham,et al.  Cancer statistics for Hispanics/Latinos, 2012 , 2012, CA: a cancer journal for clinicians.

[17]  A. Cardona,et al.  Clinical and Pathological Characteristics, Outcome and Mutational Profiles Regarding Non–Small-Cell Lung Cancer Related to Wood-Smoke Exposure , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  L. Tanoue Frequency of EGFR and KRAS Mutations in Lung Adenocarcinomas in African Americans , 2012 .

[19]  R. Rosell,et al.  Genotyping Non-small Cell Lung Cancer (NSCLC) in Latin America , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[20]  G. Bepler,et al.  Frequency and Type of Epidermal Growth Factor Receptor Mutations in African Americans with Non-small Cell Lung Cancer , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[21]  F. Cappuzzo,et al.  Genetic abnormalities of the EGFR pathway in African American Patients with non-small-cell lung cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  O. Arrieta,et al.  Wood-Smoke Exposure as a Response and Survival Predictor in Erlotinib-treated Non-small Cell Lung Cancer Patients: An Open Label Phase II Study , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[23]  Ziding Feng,et al.  Memorial Sloan-Kettering Cancer , 2006 .

[24]  J. Minna,et al.  Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. , 2006, Journal of the National Cancer Institute.

[25]  R. Wilson,et al.  EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[27]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[28]  N. Thelwell,et al.  Mode of action and application of Scorpion primers to mutation detection. , 2000, Nucleic acids research.

[29]  C Summers,et al.  Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). , 1989, Nucleic acids research.