Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma
Background: A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. Methods: Patients received cabozantinib 100 mg daily during a 12-week...
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| Veröffentlicht in: | British journal of cancer 2017-02, Vol.116 (4), p.432-440 |
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| creator | Daud, Adil Kluger, Harriet M Kurzrock, Razelle Schimmoller, Frauke Weitzman, Aaron L Samuel, Thomas A Moussa, Ali H Gordon, Michael S Shapiro, Geoffrey I |
| description | Background:
A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma.
Methods:
Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS).
Results:
Seventy-seven patients were enroled (62% cutaneous, 30% uveal, and 8% mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of evaluable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59;
P
=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most common grade 3/4 adverse events were fatigue (14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation.
Conclusions:
Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted. |
| doi_str_mv | 10.1038/bjc.2016.419 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5318966</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1872832964</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-d8bb8937e7fa3db14dd10479179f40e1a73662df66b7ddf22ae158b10b7b12693</originalsourceid><addsrcrecordid>eNqNkT1vFDEQhi1ERI5AR40s0VCwF3_s-aNBQtElnJQoKQKtZa-9OZ927cP2IpFfH68uRAFRUHnseeb1zLwAvMNoiREVp2bXLQnCbNli-QIs8IqSBgvCX4IFQog3SBJ0DF7nvKtXiQR_BY6JqKUM4wXY32x1dnCzgUkHG0efnYXW5y6G4sOki48BluT1AGMPy9bBq_Xt6ff1xTlMrnP7EhP0YeuNn6NOm3iv50pv6jMcXdG5VJGuhoMOcdRvwFGvh-zePp4n4Nv5-vbsa3N5fbE5-3LZdK2gpbHCGCEpd7zX1BrcWotRyyXmsm-Rw5pTxojtGTPc2p4Q7fBKGIwMN5gwSU_A54PufjKjs50LJelB7ZMfdfqlovbqz0zwW3UXf6oVxUIyVgU-Pgqk-GNyuai6nM4NdQwXp6yw4ERQIln7HyirzRFK57Y-_IXu4pRC3cRMiarIuajUpwPVpZhzcv1T3xip2XVVXVez66q6XvH3z2d9gn_bXIHmAOSaCncuPfv1X4IPodi39w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1868283778</pqid></control><display><type>article</type><title>Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Daud, Adil ; Kluger, Harriet M ; Kurzrock, Razelle ; Schimmoller, Frauke ; Weitzman, Aaron L ; Samuel, Thomas A ; Moussa, Ali H ; Gordon, Michael S ; Shapiro, Geoffrey I</creator><creatorcontrib>Daud, Adil ; Kluger, Harriet M ; Kurzrock, Razelle ; Schimmoller, Frauke ; Weitzman, Aaron L ; Samuel, Thomas A ; Moussa, Ali H ; Gordon, Michael S ; Shapiro, Geoffrey I</creatorcontrib><description>Background:
A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma.
Methods:
Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS).
Results:
Seventy-seven patients were enroled (62% cutaneous, 30% uveal, and 8% mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of evaluable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59;
P
=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most common grade 3/4 adverse events were fatigue (14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation.
Conclusions:
Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2016.419</identifier><identifier>PMID: 28103611</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308/2779/777 ; 692/4028/67/1813/1634 ; 692/700/565/1436/99 ; Adult ; Aged ; Aged, 80 and over ; Anilides - therapeutic use ; Antineoplastic Agents - therapeutic use ; Belgium - epidemiology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cancer therapies ; Clinical Study ; Drug Resistance ; Epidemiology ; Female ; Hematology ; Humans ; Israel - epidemiology ; Kinases ; Male ; Medical prognosis ; Melanoma ; Melanoma - drug therapy ; Melanoma - mortality ; Melanoma - pathology ; Metastasis ; Middle Aged ; Molecular Medicine ; Mutation ; Neoplasm Metastasis ; Oncology ; Proteins ; Proto-Oncogene Proteins c-met - antagonists & inhibitors ; Pyridines - therapeutic use ; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors ; Skin cancer ; Skin Neoplasms - drug therapy ; Skin Neoplasms - pathology ; Survival Analysis ; United States - epidemiology ; Uveal Neoplasms - drug therapy ; Uveal Neoplasms - mortality ; Uveal Neoplasms - pathology ; Vascular endothelial growth factor ; Withholding Treatment - statistics & numerical data</subject><ispartof>British journal of cancer, 2017-02, Vol.116 (4), p.432-440</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Feb 14, 2017</rights><rights>Copyright © 2017 The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-d8bb8937e7fa3db14dd10479179f40e1a73662df66b7ddf22ae158b10b7b12693</citedby><cites>FETCH-LOGICAL-c483t-d8bb8937e7fa3db14dd10479179f40e1a73662df66b7ddf22ae158b10b7b12693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318966/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318966/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,41467,42536,51298,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28103611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Daud, Adil</creatorcontrib><creatorcontrib>Kluger, Harriet M</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><creatorcontrib>Schimmoller, Frauke</creatorcontrib><creatorcontrib>Weitzman, Aaron L</creatorcontrib><creatorcontrib>Samuel, Thomas A</creatorcontrib><creatorcontrib>Moussa, Ali H</creatorcontrib><creatorcontrib>Gordon, Michael S</creatorcontrib><creatorcontrib>Shapiro, Geoffrey I</creatorcontrib><title>Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma.
Methods:
Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS).
Results:
Seventy-seven patients were enroled (62% cutaneous, 30% uveal, and 8% mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of evaluable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59;
P
=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most common grade 3/4 adverse events were fatigue (14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation.
Conclusions:
Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted.</description><subject>692/308/2779/777</subject><subject>692/4028/67/1813/1634</subject><subject>692/700/565/1436/99</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anilides - therapeutic use</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Belgium - epidemiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Clinical Study</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Israel - epidemiology</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - mortality</subject><subject>Melanoma - pathology</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-met - antagonists & inhibitors</subject><subject>Pyridines - therapeutic use</subject><subject>Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - pathology</subject><subject>Survival Analysis</subject><subject>United States - epidemiology</subject><subject>Uveal Neoplasms - drug therapy</subject><subject>Uveal Neoplasms - mortality</subject><subject>Uveal Neoplasms - pathology</subject><subject>Vascular endothelial growth factor</subject><subject>Withholding Treatment - statistics & numerical data</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkT1vFDEQhi1ERI5AR40s0VCwF3_s-aNBQtElnJQoKQKtZa-9OZ927cP2IpFfH68uRAFRUHnseeb1zLwAvMNoiREVp2bXLQnCbNli-QIs8IqSBgvCX4IFQog3SBJ0DF7nvKtXiQR_BY6JqKUM4wXY32x1dnCzgUkHG0efnYXW5y6G4sOki48BluT1AGMPy9bBq_Xt6ff1xTlMrnP7EhP0YeuNn6NOm3iv50pv6jMcXdG5VJGuhoMOcdRvwFGvh-zePp4n4Nv5-vbsa3N5fbE5-3LZdK2gpbHCGCEpd7zX1BrcWotRyyXmsm-Rw5pTxojtGTPc2p4Q7fBKGIwMN5gwSU_A54PufjKjs50LJelB7ZMfdfqlovbqz0zwW3UXf6oVxUIyVgU-Pgqk-GNyuai6nM4NdQwXp6yw4ERQIln7HyirzRFK57Y-_IXu4pRC3cRMiarIuajUpwPVpZhzcv1T3xip2XVVXVez66q6XvH3z2d9gn_bXIHmAOSaCncuPfv1X4IPodi39w</recordid><startdate>20170214</startdate><enddate>20170214</enddate><creator>Daud, Adil</creator><creator>Kluger, Harriet M</creator><creator>Kurzrock, Razelle</creator><creator>Schimmoller, Frauke</creator><creator>Weitzman, Aaron L</creator><creator>Samuel, Thomas A</creator><creator>Moussa, Ali H</creator><creator>Gordon, Michael S</creator><creator>Shapiro, Geoffrey I</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170214</creationdate><title>Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma</title><author>Daud, Adil ; Kluger, Harriet M ; Kurzrock, Razelle ; Schimmoller, Frauke ; Weitzman, Aaron L ; Samuel, Thomas A ; Moussa, Ali H ; Gordon, Michael S ; Shapiro, Geoffrey I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-d8bb8937e7fa3db14dd10479179f40e1a73662df66b7ddf22ae158b10b7b12693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>692/308/2779/777</topic><topic>692/4028/67/1813/1634</topic><topic>692/700/565/1436/99</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anilides - therapeutic use</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Belgium - epidemiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Clinical Study</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Israel - epidemiology</topic><topic>Kinases</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Melanoma</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - mortality</topic><topic>Melanoma - pathology</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Oncology</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-met - antagonists & inhibitors</topic><topic>Pyridines - therapeutic use</topic><topic>Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - pathology</topic><topic>Survival Analysis</topic><topic>United States - epidemiology</topic><topic>Uveal Neoplasms - drug therapy</topic><topic>Uveal Neoplasms - mortality</topic><topic>Uveal Neoplasms - pathology</topic><topic>Vascular endothelial growth factor</topic><topic>Withholding Treatment - statistics & numerical data</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daud, Adil</creatorcontrib><creatorcontrib>Kluger, Harriet M</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><creatorcontrib>Schimmoller, Frauke</creatorcontrib><creatorcontrib>Weitzman, Aaron L</creatorcontrib><creatorcontrib>Samuel, Thomas A</creatorcontrib><creatorcontrib>Moussa, Ali H</creatorcontrib><creatorcontrib>Gordon, Michael S</creatorcontrib><creatorcontrib>Shapiro, Geoffrey I</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daud, Adil</au><au>Kluger, Harriet M</au><au>Kurzrock, Razelle</au><au>Schimmoller, Frauke</au><au>Weitzman, Aaron L</au><au>Samuel, Thomas A</au><au>Moussa, Ali H</au><au>Gordon, Michael S</au><au>Shapiro, Geoffrey I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2017-02-14</date><risdate>2017</risdate><volume>116</volume><issue>4</issue><spage>432</spage><epage>440</epage><pages>432-440</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma.
Methods:
Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS).
Results:
Seventy-seven patients were enroled (62% cutaneous, 30% uveal, and 8% mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of evaluable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59;
P
=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most common grade 3/4 adverse events were fatigue (14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation.
Conclusions:
Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28103611</pmid><doi>10.1038/bjc.2016.419</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2017-02, Vol.116 (4), p.432-440 |
| issn | 0007-0920 1532-1827 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 692/308/2779/777 692/4028/67/1813/1634 692/700/565/1436/99 Adult Aged Aged, 80 and over Anilides - therapeutic use Antineoplastic Agents - therapeutic use Belgium - epidemiology Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Clinical Study Drug Resistance Epidemiology Female Hematology Humans Israel - epidemiology Kinases Male Medical prognosis Melanoma Melanoma - drug therapy Melanoma - mortality Melanoma - pathology Metastasis Middle Aged Molecular Medicine Mutation Neoplasm Metastasis Oncology Proteins Proto-Oncogene Proteins c-met - antagonists & inhibitors Pyridines - therapeutic use Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors Skin cancer Skin Neoplasms - drug therapy Skin Neoplasms - pathology Survival Analysis United States - epidemiology Uveal Neoplasms - drug therapy Uveal Neoplasms - mortality Uveal Neoplasms - pathology Vascular endothelial growth factor Withholding Treatment - statistics & numerical data |
| title | Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma |
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