A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer
Year: 2017
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: // Sheila X. Soh 1, * , Fahad J. Siddiqui 2, 3, * , John C. Allen 2 , Go Woon Kim 4 , Jae Cheol Lee 5 , Yasushi Yatabe 6 , Manabu Soda 7 , Hiroyuki Mano 7 , Ross A. Soo 8, 9 , Tan-Min Chin 8, 9 , Hiromichi Ebi 10 , Seiji Yano 10 , Keitaro Matsuo 11 , Xiaomin Niu 12 , Shun Lu 12 , Kazutoshi Isobe 13 , Jih-Hsiang Lee 14 , James C. Yang 15 , Mingchuan Zhao 16 , Caicun Zhou 16 , June-Koo Lee 17 , Se-Hoon Lee 18 , Ji Yun Lee 18 , Myung-Ju Ahn 18 , Tira J. Tan 19 , Daniel S. Tan 19 , Eng-Huat Tan 19 , S. Tiong Ong 1, 19, 20, 21 and Wan-Teck Lim 19 1 Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 2 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 3 Centre for Global Child Health, Sick Kids Hospital, Toronto, Canada 4 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea 5 Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea 6 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan 7 Department of Cellular Signaling, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 8 Department of Haematology-Oncology, National University Cancer Institute, Singapore 9 Cancer Science Institute, National University of Singapore, Singapore 10 Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan 11 Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan 12 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 13 Department of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan 14 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan 15 Department of Oncology, Graduate Institute of Oncology and Cancer Research Centre, National Taiwan University Hospital, Taipei, Taiwan 16 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 17 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea 18 Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 19 Division of Medical Oncology, National Cancer Centre, Singapore 20 Department of Haematology, Singapore General Hospital, Singapore 21 Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA * These authors contributed equally to this work Correspondence to: Wan-Teck Lim, email: [email protected] S. Tiong Ong, email: [email protected] Keywords: BIM, polymorphism, tyrosine kinase inhibitor, lung cancer, drug resistance Received: February 21, 2017 Accepted: March 30, 2017 Published: April 13, 2017 ABSTRACT Background: A germline deletion in the BIM ( BCL2L11 ) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. Results: In an aggregate data meta-analysis ( n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06–2.13, P = 0.02). Using individual patient data ( n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251–2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603–4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063–1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. Materials and Methods: 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. Conclusions: In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM -dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.
Source: Oncotarget
Authors: Sheila X. Soh, Fahad J. Siddiqui, John C. Allen, Go Woon Kim, Jae Cheol Lee, Yasushi Yatabe, Manabu Soda, Hiroyuki Mano, Ross A. Soo, Tan-Min Chin, Hiromichi Ebi, Seiji Yano, Keitaro Matsuo, Xiaomin Niu, Shun Lu, Kazutoshi Isobe, Jih-Hsiang Lee, James C. Yang, Mingchuan Zhao, Caicun Zhou, June-Koo Lee, Se-Hoon Lee, Ji Yun Lee, Myung-Ju Ahn, Tira J. Tan, Daniel S. Tan, Eng-Huat Tan, S. Tiong Ong, Wan-Teck Lim
Institutions: Duke-NUS Medical School, Hospital for Sick Children, Asan Medical Center, University of Ulsan, Seoul National University, Samsung Medical Center, Seoul National University Hospital, National Taiwan University Hospital, Sungkyunkwan University, Aichi Cancer Center, The University of Tokyo, National University of Singapore, National University Cancer Institute, Singapore, Cancer Science Institute of Singapore, Kanazawa University, Cancer Research Institute of Kanazawa University, Aichi Cancer Center Research Institute, Shanghai Jiao Tong University, Shanghai Chest Hospital, Toho University Omori Medical Center, Tongji University, Shanghai Pulmonary Hospital, National Cancer Centre Singapore, Singapore General Hospital, Duke Medical Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2605851135