Andrés F Cardona1,2,3, Oscar Arrieta4, Martín Ignacio Zapata5, Leonardo Rojas6, Beatriz Wills7, Noemí Reguart8, Niki Karachaliou9, Hernán Carranza10,7, Carlos Vargas10,7, Jorge Otero10,7, Pilar Archila7, Claudio Martín11, Luis Corrales12, Mauricio Cuello13, Carlos Ortiz10, Luis E Pino14, Rafael Rosell15, Zyanya Lucia Zatarain-Barrón4. 1. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 2. Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 3. Internal Medicine Department, Universidad El Bosque- Fundación Santa Fe de Bogotá, Bogotá, Colombia. andres.cardona@clinicadelcountry.com. 4. Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología (INCan), México City, México. 5. Internal Medicine Department, Universidad El Bosque- Fundación Santa Fe de Bogotá, Bogotá, Colombia. 6. Medical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia. 7. Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia. 8. Medical Oncology, Hospital Clinic, Barcelona and Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 9. Translational Research Unit, IOR/Dexeus, University Hospital, Barcelona, Spain. 10. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia. 11. Medical Oncology Department, Thoracic Oncology Unit, Instituto Flemin, Buenos Aires, Argentina. 12. Medical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica. 13. Medical Oncology Department, UdeLAR, Montevideo, Uruguay. 14. Clinical Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia. 15. Medical Oncology Department, Catalan Institute of Oncology-ICO, Barcelona, Spain.
Abstract
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. RESULTS: Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). CONCLUSIONS: Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
BACKGROUND:Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFRT790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancerpatients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancerpatients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. RESULTS: Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). CONCLUSIONS: Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
Authors: Oscar Arrieta; Andrés F Cardona; Claudio Martín; Luis Más-López; Luis Corrales-Rodríguez; Guillermo Bramuglia; Omar Castillo-Fernandez; Matthew Meyerson; Eduardo Amieva-Rivera; Alma Delia Campos-Parra; Hernán Carranza; Juan Carlos Gómez de la Torre; Yanina Powazniak; Fernando Aldaco-Sarvide; Carlos Vargas; Mariana Trigo; Manuel Magallanes-Maciel; Jorge Otero; Roberto Sánchez-Reyes; Mauricio Cuello Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609
Authors: David Jackman; William Pao; Gregory J Riely; Jeffrey A Engelman; Mark G Kris; Pasi A Jänne; Thomas Lynch; Bruce E Johnson; Vincent A Miller Journal: J Clin Oncol Date: 2009-11-30 Impact factor: 44.544