151. BIM deletion polymorphisms in hispanic patients with non-small cell lung cancer carriers of EGFR mutations
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Carlos Vargas, Hernán Carranza, Sandra Franco, Beatriz Wills, Christian Rolfo, Claudio Martin, Leonardo Rojas, Carlos Ortiz, Noemi Reguart, L. Corrales-Rodriguez, Andrés F. Cardona, July Rodriguez, Jorge Otero, Rafael Rosell, Mauricio Cuello, Oscar Arrieta, Pilar Archila, CLICAP, Cardona-Mendoza, Andrés Felipe [0000-0002-6697-5471], Carranza Isaza, Hernán [0000-0002-3593-7405], Vargas Báez, Carlos Alberto [0000-0002-6076-8260], Rojas Puentes, Leonardo [0000-0002-7865-5424], and Rodríguez Ariza, July Katherine [0000-0003-1168-595X]
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0301 basic medicine ,Gerontology ,Oncology ,Male ,Survival ,cells ,DNA Mutational Analysis ,Biomarkers, Pharmacological ,0302 clinical medicine ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Sequence Deletion ,Clinical Oncology ,Bcl-2-Like Protein 11 ,Incidence (epidemiology) ,hemic and immune systems ,Hispanic or Latino ,Middle Aged ,University hospital ,ErbB Receptors ,Proteína 11 similar a Bcl2 ,030220 oncology & carcinogenesis ,Female ,Non small cell ,Erlotinib ,biological phenomena, cell phenomena, and immunity ,medicine.drug ,Research Paper ,Risk ,medicine.medical_specialty ,Neoplasias pulmonares ,BIM deletion ,survival ,03 medical and health sciences ,Erlotinib Hydrochloride ,Asian People ,Thoracic Oncology ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Lung cancer ,neoplasms ,Biology ,non-small cell lung cancer ,Genes erbB-1 ,Polymorphism, Genetic ,business.industry ,medicine.disease ,Survival Analysis ,030104 developmental biology ,Egfr mutation ,Human medicine ,EGFR mutation ,business - Abstract
// Andres F. Cardona 1, 2, 3, * , Leonardo Rojas 4, 5, * , Beatriz Wills 2, * , Oscar Arrieta 6, * , Hernan Carranza 1, 2, 3 , Carlos Vargas 1, 2, 3 , Jorge Otero 1, 2, 3 , Luis Corrales-Rodriguez 7 , Claudio Martin 8 , Noemi Reguart 9 , Pilar Archila 2 , July Rodriguez 2 , Mauricio Cuello 10 , Carlos Ortiz 1 , Sandra Franco 1 , Christian Rolfo 11 , Rafael Rosell 12 , on behalf of the CLICaP # 1 Clinical and Traslational Oncology Group, Institute of Oncology, Clinica del Country, Bogota, Colombia 2 Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia 3 Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogota, Colombia 4 Clinical Oncology Department, Centro Javeriano de Oncologia, Hospital Universitario San Ignacio, Bogota, Colombia 5 Faculty of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia 6 Thoracic Oncology Unit, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico 7 Medical Oncology Department, Hospital San Juan de Dios, San Jose, Costa Rica 8 Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina 9 Medical Oncology Department, Hospital Clinic, Barcelona, Spain 10 Clinical Oncology Department, Hospital de Clinicas-UdeLAR, Montevideo, Uruguay 11 Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital and Center for Oncological Research (CORE), Antwerp University, Edegem, Belgium 12 Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain # Latin American Consortium for Lung Cancer Investigation * These authors have contributed equally to this study Correspondence to: Andres F. Cardona, email: andres.cardona@clinicadelcountry.com , a_cardonaz@yahoo.com Keywords: non-small cell lung cancer, BIM deletion, EGFR mutation, survival Received: February 24, 2016 Accepted: August 24, 2016 Published: September 19, 2016 ABSTRACT Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. Results: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM -del in clinical characteristics or EGFR mutation type; however, those with BIM -del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM -del ; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM -del+ vs. 21.7 months for patients without BIM -del ; p=0.029) and overall survival (OS) (15.5 BIM -del+ vs. 34.0 months for patients without BIM -del ; p=0.035). Multivariate Cox regression analysis showed that BIM -del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). Methods: We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM -del ) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM- del . Conclusions: The incidence of BIM -del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.
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- 2016