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Li-Tzong Chen,오도연,류민희,Kun-Huei Yeh,Winnie Yeo,Roberto Carlesi,Rebecca Cheng,김종석,Mauro Orlando,강윤구 대한암학회 2017 Cancer Research and Treatment Vol.49 No.4
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
( Thomas Yau ),( Tim Meyer ),( Ignacio Melero ),( Chiun Hsu ),( Masa-toshi Kudo ),( Su-pin Choo ),( Jorg Trojan ),( Theodore H. Welling ),( Yoon-koo Kang ),( Winnie Yeo ),( Akhil Chopra ),( Adyb Baaki 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Nivolumab (NIVO) is a fully human anti-PD-1 IgG4 mAb that demonstrated durable responses, manageable safety, and long-term survival in pts with advanced HCC (aHCC) in CheckMate-040 (El-Khoueiry AB et al. Lancet 2017). Here we present updated hepatic safety and biomarker analyses in sorafenib-experienced (sor-exp) pts in CheckMate-040. Methods: Sor-exp pts with or without chronic viral hepatitis received NIVO 3 mg/kg Q2W. Primary endpoint was objective response rate (ORR) reported by blinded independent central review using RECIST v1.1. Secondary endpoints included overall survival (OS), disease control rate (DCR), and safety. Exploratory analyses of on-treatment HCV and HBV viral kinetics and alpha-fetoprotein (AFP) levels were performed. Results: Median duration of follow-up was 14.9 mo. Baseline Child-Pugh scores of 5 or 6 and extrahepatic metastases were observed in 99% and 71% of pts, respectively. The ORR with NIVO was 14%; the DCR was 56%; median OS was 15.6 mo. Any-grade and grade 3-4 hepatic treatment-related AEs (TRAEs) occurred in 12 (8%) and 5 (3%) pts, respectively; 100% of grade 3-4 hepatic TRAEs resolved. Frequencies of grade 3-4 treatment-related ALT/AST elevations were 2%-3%. No drug-related deaths due to hepatic AEs occurred, and no new safety signals were observed. AFP levels at baseline were not associated with response; however, AFP levels in responders appeared to decrease on treatment. Updated data will be presented. Conclusions: NIVO demonstrated long-term survival and objective responses across etiologies and manageable overall and hepatic safety profile in aHCC. Responses occurred irrespective of baseline AFP levels, and AFP declines were associated with response.