Andrés F Cardona1, Leonardo Rojas2, Zyanya Lucia Zatarain-Barrón3, Helano C Freitas4, Sara T Granados5, Omar Castillo6, George Oblitas7, Luis Corrales8, Christian D Castro5, Alejandro Ruiz-Patiño5, Claudio Martín9, María Angelina Pérez7, Lisde González10, Luis Chirinos11, Carlos Vargas12, Hernán Carranza12, Jorge Otero12, July Rodriguez5, Jenny Rodriguez5, Pilar Archila5, Mauricio Lema13, José Acosta Madiedo14, Niki Karachaliu15, Beatriz Wills16, Luis E Pino17, Vladimir de Lima18, Rafael Rosell19, Oscar Arrieta3. 1. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia; Clinical Research and Biology Systems Department, Universidad el Bosque, Bogotá, Colombia. Electronic address: a_cardonaz@yahoo.com. 2. Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia; Clinical Research and Biology Systems Department, Universidad el Bosque, Bogotá, Colombia; Internal Medicine Department, Pontificia Universidad Javeriana, Bogotá, Colombia; Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia. 3. Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico. 4. A.C. Camargo Cancer Center, São Paulo, Brazil. 5. Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia. 6. Instituto Oncológico Nacional, Panamá City, Panama. 7. Hospital Oncológico Luis Razetti, Caracas, Venezuela. 8. Oncology Department, Hospital San Juan de Dios, San José Costa Rica, Costa Rica. 9. Medical Oncology Group, Fleming Institute, Buenos Aires, Argentina. 10. Arsuve, Caracas, Venezuela. 11. Clínica de Prevención del Cáncer, Caracas, Venezuela. 12. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia; Clinical Research and Biology Systems Department, Universidad el Bosque, Bogotá, Colombia. 13. Oncology Department, Clínica Astorga, Medellín, Colombia. 14. Oncology Department, Clínica Porto Azul, Barranquilla, Colombia. 15. Translational Research Unit, Coyote Group, IOR/Dexeus University Hospital, Barcelona, Spain. 16. Internal Medicine Department, Johns Hopkins University, Baltimore, Maryland, United States. 17. Oncology Department, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, Colombia. 18. Thoracic Oncology Unit, A.C. Camargo Cancer Center, São Paulo, Brazil. 19. Personalized Medicine Program, Catalan Institute of Oncology - ICO, Barcelona, Spain.
Abstract
OBJECTIVES: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients. MATERIALS AND METHODS: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach. RESULTS AND CONCLUSIONS: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm.
OBJECTIVES: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients. MATERIALS AND METHODS: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach. RESULTS AND CONCLUSIONS: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm.
Authors: Mohd Imran; Shah Alam Khan; Mohammed Kanan Alshammari; Meshal Ayedh Alreshidi; Abeer Abdullah Alreshidi; Rawan Sulaiman Alghonaim; Fayez Aboud Alanazi; Sultan Alshehri; Mohammed M Ghoneim; Faiyaz Shakeel Journal: Biomedicines Date: 2021-12-17