Randomized, open‐label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma
Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated f...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2016-09, Vol.64 (3), p.774-784 |
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| creator | Cheng, Ann‐Lii Thongprasert, Sumitra Lim, Ho Yeong Sukeepaisarnjaroen, Wattana Yang, Tsai‐Shen Wu, Cheng‐Chung Chao, Yee Chan, Stephen L. Kudo, Masatoshi Ikeda, Masafumi Kang, Yoon‐Koo Pan, Hongming Numata, Kazushi Han, Guohong Balsara, Binaifer Zhang, Yong Rodriguez, Ana‐Marie Zhang, Yi Wang, Yongyu Poon, Ronnie T. P. |
| description | Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open‐label, randomized phase 2 study of Asian‐Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6‐9.1) months for dovitinib and 8.4 (5.4‐11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8‐4.2) months and 4.1 (2.8‐4.3) months for dovitinib and sorafenib, respectively. Common any‐cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar‐plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0‐13.8] and 5.7 [4.3‐7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9‐13.8] and 5.9 [5.0‐7.6] months, respectively [P = 0.0002]). Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774‐784) |
| doi_str_mv | 10.1002/hep.28600 |
| format | Article |
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P.</creator><creatorcontrib>Cheng, Ann‐Lii ; Thongprasert, Sumitra ; Lim, Ho Yeong ; Sukeepaisarnjaroen, Wattana ; Yang, Tsai‐Shen ; Wu, Cheng‐Chung ; Chao, Yee ; Chan, Stephen L. ; Kudo, Masatoshi ; Ikeda, Masafumi ; Kang, Yoon‐Koo ; Pan, Hongming ; Numata, Kazushi ; Han, Guohong ; Balsara, Binaifer ; Zhang, Yong ; Rodriguez, Ana‐Marie ; Zhang, Yi ; Wang, Yongyu ; Poon, Ronnie T. P.</creatorcontrib><description>Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open‐label, randomized phase 2 study of Asian‐Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6‐9.1) months for dovitinib and 8.4 (5.4‐11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8‐4.2) months and 4.1 (2.8‐4.3) months for dovitinib and sorafenib, respectively. Common any‐cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar‐plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0‐13.8] and 5.7 [4.3‐7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9‐13.8] and 5.9 [5.0‐7.6] months, respectively [P = 0.0002]). Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774‐784)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.28600</identifier><identifier>PMID: 27082062</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Angiogenesis ; Animals ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - therapeutic use ; Benzimidazoles - adverse effects ; Benzimidazoles - pharmacokinetics ; Benzimidazoles - therapeutic use ; Biomarkers - blood ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - mortality ; Cell Line, Tumor ; Confidence intervals ; Far East - epidemiology ; Female ; Growth factors ; Hepatology ; Humans ; Liver cancer ; Liver Neoplasms - blood ; Liver Neoplasms - drug therapy ; Liver Neoplasms - mortality ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Middle Aged ; Niacinamide - adverse effects ; Niacinamide - analogs & derivatives ; Niacinamide - pharmacokinetics ; Niacinamide - therapeutic use ; Phenylurea Compounds - adverse effects ; Phenylurea Compounds - pharmacokinetics ; Phenylurea Compounds - therapeutic use ; Quinolones - adverse effects ; Quinolones - pharmacokinetics ; Quinolones - therapeutic use ; Treatment Outcome ; Xenograft Model Antitumor Assays</subject><ispartof>Hepatology (Baltimore, Md.), 2016-09, Vol.64 (3), p.774-784</ispartof><rights>2016 by the American Association for the Study of Liver Diseases</rights><rights>2016 by the American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4910-8c90b10313cf8defb9fa40122c3cca011b2df27da6909e6cac76ec84335a6f1a3</citedby><cites>FETCH-LOGICAL-c4910-8c90b10313cf8defb9fa40122c3cca011b2df27da6909e6cac76ec84335a6f1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.28600$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.28600$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27082062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Ann‐Lii</creatorcontrib><creatorcontrib>Thongprasert, Sumitra</creatorcontrib><creatorcontrib>Lim, Ho Yeong</creatorcontrib><creatorcontrib>Sukeepaisarnjaroen, Wattana</creatorcontrib><creatorcontrib>Yang, Tsai‐Shen</creatorcontrib><creatorcontrib>Wu, Cheng‐Chung</creatorcontrib><creatorcontrib>Chao, Yee</creatorcontrib><creatorcontrib>Chan, Stephen L.</creatorcontrib><creatorcontrib>Kudo, Masatoshi</creatorcontrib><creatorcontrib>Ikeda, Masafumi</creatorcontrib><creatorcontrib>Kang, Yoon‐Koo</creatorcontrib><creatorcontrib>Pan, Hongming</creatorcontrib><creatorcontrib>Numata, Kazushi</creatorcontrib><creatorcontrib>Han, Guohong</creatorcontrib><creatorcontrib>Balsara, Binaifer</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Rodriguez, Ana‐Marie</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Wang, Yongyu</creatorcontrib><creatorcontrib>Poon, Ronnie T. P.</creatorcontrib><title>Randomized, open‐label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open‐label, randomized phase 2 study of Asian‐Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6‐9.1) months for dovitinib and 8.4 (5.4‐11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8‐4.2) months and 4.1 (2.8‐4.3) months for dovitinib and sorafenib, respectively. Common any‐cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar‐plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0‐13.8] and 5.7 [4.3‐7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9‐13.8] and 5.9 [5.0‐7.6] months, respectively [P = 0.0002]). Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774‐784)</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Benzimidazoles - adverse effects</subject><subject>Benzimidazoles - pharmacokinetics</subject><subject>Benzimidazoles - therapeutic use</subject><subject>Biomarkers - blood</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Cell Line, Tumor</subject><subject>Confidence intervals</subject><subject>Far East - epidemiology</subject><subject>Female</subject><subject>Growth factors</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - mortality</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Niacinamide - adverse effects</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Niacinamide - pharmacokinetics</subject><subject>Niacinamide - therapeutic use</subject><subject>Phenylurea Compounds - adverse effects</subject><subject>Phenylurea Compounds - pharmacokinetics</subject><subject>Phenylurea Compounds - therapeutic use</subject><subject>Quinolones - adverse effects</subject><subject>Quinolones - pharmacokinetics</subject><subject>Quinolones - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0c9qFTEUBvAgFnutLnwBCbhRcNqTzN8sS6m2UKiIroczyRlvykwyJjO3XFcuXfqMPom5vdWFUHAVOPz4ODkfYy8EHAsAebKm6Vg2FcAjthKlrLM8L-ExW4GsIVMiV4fsaYw3AKAK2Txhh2neSKjkiv34iM740X4j85b7idyv7z8H7Gjg0xojccnjvJgt136cMFj3hffBu3mwjrjxGztbZzu-oRCXyKMP2NNuYB2fcLbk5shv7bzmaDboNBmedsXZaxqGZcDANQZtnR_xGTvocYj0_P49Yp_fnX86u8iurt9fnp1eZbpQArJGK-gE5CLXfWOo71SPBQgpda41ghCdNL2sDVYKFFUadV2Rbop0Eax6gfkRe73PnYL_ulCc29HG3TroyC-xFY0o65QnxP9Q2TSlFCrRV__QG78Elz5yp0pQVbFTb_ZKBx9joL6dgh0xbFsB7a7JNl2nvWsy2Zf3iUs3kvkr_1SXwMke3NqBtg8ntRfnH_aRvwEbqKqj</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Cheng, Ann‐Lii</creator><creator>Thongprasert, Sumitra</creator><creator>Lim, Ho Yeong</creator><creator>Sukeepaisarnjaroen, Wattana</creator><creator>Yang, Tsai‐Shen</creator><creator>Wu, Cheng‐Chung</creator><creator>Chao, Yee</creator><creator>Chan, Stephen L.</creator><creator>Kudo, Masatoshi</creator><creator>Ikeda, Masafumi</creator><creator>Kang, Yoon‐Koo</creator><creator>Pan, Hongming</creator><creator>Numata, Kazushi</creator><creator>Han, Guohong</creator><creator>Balsara, Binaifer</creator><creator>Zhang, Yong</creator><creator>Rodriguez, Ana‐Marie</creator><creator>Zhang, Yi</creator><creator>Wang, Yongyu</creator><creator>Poon, Ronnie T. 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P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4910-8c90b10313cf8defb9fa40122c3cca011b2df27da6909e6cac76ec84335a6f1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Benzimidazoles - adverse effects</topic><topic>Benzimidazoles - pharmacokinetics</topic><topic>Benzimidazoles - therapeutic use</topic><topic>Biomarkers - blood</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Cell Line, Tumor</topic><topic>Confidence intervals</topic><topic>Far East - epidemiology</topic><topic>Female</topic><topic>Growth factors</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - mortality</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Niacinamide - adverse effects</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Niacinamide - pharmacokinetics</topic><topic>Niacinamide - therapeutic use</topic><topic>Phenylurea Compounds - adverse effects</topic><topic>Phenylurea Compounds - pharmacokinetics</topic><topic>Phenylurea Compounds - therapeutic use</topic><topic>Quinolones - adverse effects</topic><topic>Quinolones - pharmacokinetics</topic><topic>Quinolones - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Ann‐Lii</creatorcontrib><creatorcontrib>Thongprasert, Sumitra</creatorcontrib><creatorcontrib>Lim, Ho Yeong</creatorcontrib><creatorcontrib>Sukeepaisarnjaroen, Wattana</creatorcontrib><creatorcontrib>Yang, Tsai‐Shen</creatorcontrib><creatorcontrib>Wu, Cheng‐Chung</creatorcontrib><creatorcontrib>Chao, Yee</creatorcontrib><creatorcontrib>Chan, Stephen L.</creatorcontrib><creatorcontrib>Kudo, Masatoshi</creatorcontrib><creatorcontrib>Ikeda, Masafumi</creatorcontrib><creatorcontrib>Kang, Yoon‐Koo</creatorcontrib><creatorcontrib>Pan, Hongming</creatorcontrib><creatorcontrib>Numata, Kazushi</creatorcontrib><creatorcontrib>Han, Guohong</creatorcontrib><creatorcontrib>Balsara, Binaifer</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Rodriguez, Ana‐Marie</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Wang, Yongyu</creatorcontrib><creatorcontrib>Poon, Ronnie T. P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Ann‐Lii</au><au>Thongprasert, Sumitra</au><au>Lim, Ho Yeong</au><au>Sukeepaisarnjaroen, Wattana</au><au>Yang, Tsai‐Shen</au><au>Wu, Cheng‐Chung</au><au>Chao, Yee</au><au>Chan, Stephen L.</au><au>Kudo, Masatoshi</au><au>Ikeda, Masafumi</au><au>Kang, Yoon‐Koo</au><au>Pan, Hongming</au><au>Numata, Kazushi</au><au>Han, Guohong</au><au>Balsara, Binaifer</au><au>Zhang, Yong</au><au>Rodriguez, Ana‐Marie</au><au>Zhang, Yi</au><au>Wang, Yongyu</au><au>Poon, Ronnie T. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Randomized, open‐label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2016-09</date><risdate>2016</risdate><volume>64</volume><issue>3</issue><spage>774</spage><epage>784</epage><pages>774-784</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open‐label, randomized phase 2 study of Asian‐Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6‐9.1) months for dovitinib and 8.4 (5.4‐11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8‐4.2) months and 4.1 (2.8‐4.3) months for dovitinib and sorafenib, respectively. Common any‐cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar‐plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0‐13.8] and 5.7 [4.3‐7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9‐13.8] and 5.9 [5.0‐7.6] months, respectively [P = 0.0002]). Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774‐784)</abstract><cop>United States</cop><pub>Wolters Kluwer Health, Inc</pub><pmid>27082062</pmid><doi>10.1002/hep.28600</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Hepatology (Baltimore, Md.), 2016-09, Vol.64 (3), p.774-784 |
| issn | 0270-9139 1527-3350 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1815712211 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Aged Aged, 80 and over Angiogenesis Animals Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - therapeutic use Benzimidazoles - adverse effects Benzimidazoles - pharmacokinetics Benzimidazoles - therapeutic use Biomarkers - blood Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - mortality Cell Line, Tumor Confidence intervals Far East - epidemiology Female Growth factors Hepatology Humans Liver cancer Liver Neoplasms - blood Liver Neoplasms - drug therapy Liver Neoplasms - mortality Male Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Middle Aged Niacinamide - adverse effects Niacinamide - analogs & derivatives Niacinamide - pharmacokinetics Niacinamide - therapeutic use Phenylurea Compounds - adverse effects Phenylurea Compounds - pharmacokinetics Phenylurea Compounds - therapeutic use Quinolones - adverse effects Quinolones - pharmacokinetics Quinolones - therapeutic use Treatment Outcome Xenograft Model Antitumor Assays |
| title | Randomized, open‐label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T01%3A53%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Randomized,%20open%E2%80%90label%20phase%202%20study%20comparing%20frontline%20dovitinib%20versus%20sorafenib%20in%20patients%20with%20advanced%20hepatocellular%20carcinoma&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=Cheng,%20Ann%E2%80%90Lii&rft.date=2016-09&rft.volume=64&rft.issue=3&rft.spage=774&rft.epage=784&rft.pages=774-784&rft.issn=0270-9139&rft.eissn=1527-3350&rft.coden=HPTLD9&rft_id=info:doi/10.1002/hep.28600&rft_dat=%3Cproquest_cross%3E1815712211%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1812509649&rft_id=info:pmid/27082062&rfr_iscdi=true |