PMID- 28870253 OWN - NLM STAT- MEDLINE DCOM- 20180615 LR - 20220331 IS - 1756-8722 (Electronic) IS - 1756-8722 (Linking) VI - 10 IP - 1 DP - 2017 Sep 5 TI - Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study. PG - 153 LID - 10.1186/s13045-017-0521-0 [doi] LID - 153 AB - BACKGROUND: Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. PATIENTS AND METHODS: We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan-Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival. RESULTS: Presence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64-0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53-0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival. CONCLUSION: Presence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients. FAU - Liu, Xinyang AU - Liu X AD - Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. AD - Fudan University Zhongshan Hospital, Shanghai, China. FAU - Qin, Shukui AU - Qin S AD - People's Liberation Army Cancer Center, 81st Hospital of People's Liberation Army, Beijing, China. FAU - Wang, Zhichao AU - Wang Z AD - Fudan University Zhongshan Hospital, Shanghai, China. FAU - Xu, Jianming AU - Xu J AD - Academy of Military Medical Sciences, 307th Hospital of PLA, Beijing, China. FAU - Xiong, Jianping AU - Xiong J AD - First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Bai, Yuxian AU - Bai Y AD - Harbin Medical University Cancer Hospital, Harbin, China. FAU - Wang, Zhehai AU - Wang Z AD - Shandong Cancer Hospital, Jinan, China. FAU - Yang, Yan AU - Yang Y AD - Gansu Cancer Hospital, Lanzhou, China. FAU - Sun, Guoping AU - Sun G AD - First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Wang, Liwei AU - Wang L AD - Shanghai First People's Hospital, Shanghai, China. FAU - Zheng, Leizhen AU - Zheng L AD - XinHua Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. FAU - Xu, Nong AU - Xu N AD - First Affiliated Hospital of Zhejiang University, Hangzhou, China. FAU - Cheng, Ying AU - Cheng Y AD - Jilin Provincial Cancer Hospital, Changchun, China. FAU - Guo, Weijian AU - Guo W AD - Fudan University Shanghai Cancer Center, Shanghai, China. FAU - Yu, Hao AU - Yu H AD - Nanjing Medical University, Nanjing, China. FAU - Liu, Tianshu AU - Liu T AD - Fudan University Zhongshan Hospital, Shanghai, China. FAU - Lagiou, Pagona AU - Lagiou P AD - Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. plagiou@hsph.harvard.edu. AD - Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 75 M. Asias Street, Goudi GR, 115 27, Athens, Greece. plagiou@hsph.harvard.edu. FAU - Li, Jin AU - Li J AD - Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. fudanlijin@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170905 PL - England TA - J Hematol Oncol JT - Journal of hematology & oncology JID - 101468937 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Biomarkers, Tumor) RN - 0 (Pyridines) RN - 5S371K6132 (apatinib) SB - IM EIN - J Hematol Oncol. 2018 Jan 9;11(1):5. PMID: 29316953 MH - Adult MH - Aged MH - Angiogenesis Inhibitors/*adverse effects MH - Biomarkers, Tumor/*metabolism MH - Cohort Studies MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Pyridines/*adverse effects MH - Retrospective Studies MH - Stomach Neoplasms/*complications/*drug therapy MH - Treatment Outcome PMC - PMC5584332 OTO - NOTNLM OT - Adverse events OT - Apatinib OT - Biomarker OT - Gastric cancer COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was determined as Not Human Subjects Research by Harvard T. H. Chan School of Public Health Office of Human Research Administration (IRB16-1248, 08/04/2016). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/09/06 06:00 MHDA- 2018/06/16 06:00 PMCR- 2017/09/05 CRDT- 2017/09/06 06:00 PHST- 2017/05/18 00:00 [received] PHST- 2017/08/28 00:00 [accepted] PHST- 2017/09/06 06:00 [entrez] PHST- 2017/09/06 06:00 [pubmed] PHST- 2018/06/16 06:00 [medline] PHST- 2017/09/05 00:00 [pmc-release] AID - 10.1186/s13045-017-0521-0 [pii] AID - 521 [pii] AID - 10.1186/s13045-017-0521-0 [doi] PST - epublish SO - J Hematol Oncol. 2017 Sep 5;10(1):153. doi: 10.1186/s13045-017-0521-0.