Alejandro Ruiz-Patiño1, Christian David Castro1, Luisa María Ricaurte1, Andrés F Cardona2,3,4, Leonardo Rojas5,6, Zyanya Lucia Zatarain-Barrón7, Beatriz Wills8, Noemí Reguart9, Hernán Carranza1,5, Carlos Vargas1,5, Jorge Otero1,5, Luis Corrales10, Claudio Martín11, Pilar Archila1, July Rodriguez1, Jenny Avila1, Melissa Bravo1, Luis Eduardo Pino12, Rafael Rosell13, Oscar Arrieta7. 1. Foundation for Clinical and Applied Cancer Research (FICMAC), Calle 116 No. 9-72, c. 318, Bogotá, Colombia. 2. Foundation for Clinical and Applied Cancer Research (FICMAC), Calle 116 No. 9-72, c. 318, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 3. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 4. Molecular Oncology and Biology Systems Research Group (FOX-G), Universidad El Bosque, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 5. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia. 6. Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia. 7. Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. 8. Internal Medicine Department, Johns Hopkins University, Baltimore, MD, USA. 9. Medical Oncology Department, Hospital Clinic, Barcelona, Spain. 10. Clinical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica. 11. Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina. 12. Medical Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia. 13. Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp. PATIENTS AND METHODS: Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status. RESULTS: 30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3-34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7) vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043). CONCLUSION: Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.
BACKGROUND:Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp. PATIENTS AND METHODS: Seventy-two EGFR-positive lung adenocarcinomapatients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status. RESULTS: 30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3-34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7) vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043). CONCLUSION: Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.
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