Kudo, Masatoshi; Kang, Yoon-Koo; Park, Joong-Won; Qin, Shukui; Inaba, Yoshitaka; Assenat, Eric; Umeyama, Yoshiko; Lechuga, Maria Jose; Valota, Olga; Fujii, Yosuke; Martini, Jean-Francois; Williams, J Andrew; Obi, Shuntaro
Liver cancer
2018May ; 7 ( 2 ) :148-164.
PMID : 29888205
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Kudo, Masatoshi - Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Kang, Yoon-Koo - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Park, Joong-Won - Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea.
Qin, Shukui - Department of Medical Oncology, Nanjing Bayi Hospital, Nanjing, China.
Inaba, Yoshitaka - Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan.
Assenat, Eric - Department of Medical Oncology, Hopital Saint Eloi, Montpellier, France.
Umeyama, Yoshiko - Pfizer Japan Inc., Tokyo, Japan.
Lechuga, Maria Jose - Pfizer Srl, Milan, Italy.
Valota, Olga - Pfizer Srl, Milan, Italy.
Fujii, Yosuke - Pfizer Japan Inc., Tokyo, Japan.
Martini, Jean-Francois - Pfizer Inc., San Diego, CA, USA.
Williams, J Andrew - Pfizer Inc., San Diego, CA, USA.
Obi, Shuntaro - Department of Hepatology, Sasaki Foundation Kyoundo Hospital, Tokyo, Japan.
ABSTRACT
BACKGROUND: An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial (ClinicalTrial.gov No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors.
METHODS: The data from this phase II study were analyzed for the efficacy and safety of axitinib/BSC in patients from Asia versus non-Asia versus Asian subgroups (Japan, Korea, or mainland China/Hong Kong/Taiwan) and predictive/prognostic values of baseline microRNAs and serum soluble proteins, using the Cox proportional hazards model.
RESULTS: Of 202 patients, 78 were from non-Asia and 124 from Asia (37 Japanese, 36 Korean, and 51 Chinese). No significant differences in OS were found between axitinib/BSC and placebo/BSC in non-Asians, Asians, or Asian subgroups. However, in an exploratory analysis, axitinib/BSC showed favorable OS in Asians, especially Japanese, when patients intolerant to prior antiangiogenic therapy were excluded from the data set. Axitinib/BSC was well tolerated by non-Asians and Asians alike. The presence of 4 circulating microRNAs, including miR-5684 and miR-1224-5p, or a level lower than or equal to the median protein level of stromal cell-derived factor 1 at baseline was significantly associated with longer OS in axitinib/BSC-treated Asians or non-Asians.
CONCLUSIONS: Axitinib/BSC did not prolong survival over placebo/BSC in non-Asians, Asians, or Asian subgroups, but favorable OS with axitinib/BSC was observed in a subset of Japanese patients. A patient population that excludes sorafenib-intolerant patients might potentially be more suitable for clinical trials of new agents in advanced HCC. Since these results are very preliminary, further investigation is warranted. The potential predictive/prognostic value of several baseline microRNAs and soluble proteins identified in this study would require validation in prospective studies on a large cohort of patients.
keyword
*Asian; *Axitinib; *Biomarkers; *Hepatocellular carcinoma; *MicroRNAs
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