Research Papers:

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

Andrés F. Cardona _, Leonardo Rojas, Beatriz Wills, Oscar Arrieta, Hernán Carranza, Carlos Vargas, Jorge Otero, Luis Corrales-Rodriguez, Claudio Martín, Noemí Reguart, Pilar Archila, July Rodríguez, Mauricio Cuello, Carlos Ortíz, Sandra Franco, Christian Rolfo, Rafael Rosell and on behalf of the CLICaP

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Oncotarget. 2016; 7:68933-68942. https://doi.org/10.18632/oncotarget.12112

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Andrés F. Cardona1,2,3,*, Leonardo Rojas4,5,*, Beatriz Wills2,*, Oscar Arrieta6,*, Hernán Carranza1,2,3, Carlos Vargas1,2,3, Jorge Otero1,2,3, Luis Corrales-Rodriguez7, Claudio Martín8, Noemí Reguart9, Pilar Archila2, July Rodríguez2, Mauricio Cuello10, Carlos Ortíz1, Sandra Franco1, Christian Rolfo11, Rafael Rosell12, on behalf of the CLICaP#

1Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia

2Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia

3Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogotá, Colombia

4Clinical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá, Colombia

5Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia

6Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México

7Medical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica

8Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina

9Medical Oncology Department, Hospital Clínic, Barcelona, Spain

10Clinical Oncology Department, Hospital de Clínicas-UdeLAR, Montevideo, Uruguay

11Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital and Center for Oncological Research (CORE), Antwerp University, Edegem, Belgium

12Medical 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:

Andrés F. Cardona, email: [email protected], [email protected]

Keywords: non-small cell lung cancer, BIM deletion, EGFR mutation, survival

Received: February 24, 2016    Accepted: August 24, 2016    Published: September 19, 2016


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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