A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses
Purpose Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women wit...
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| Veröffentlicht in: | Breast cancer research and treatment 2008-12, Vol.112 (3), p.533-543 |
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| creator | Cameron, David Casey, Michelle Press, Michael Lindquist, Deborah Pienkowski, Tadeusz Romieu, C. Gilles Chan, Stephen Jagiello-Gruszfeld, Agnieszka Kaufman, Bella Crown, John Chan, Arlene Campone, Mario Viens, Patrice Davidson, Neville Gorbounova, Vera Raats, Johannes Isaac Skarlos, Dimosthenis Newstat, Beth Roychowdhury, Debasish Paoletti, Paolo Oliva, Cristina Rubin, Stephen Stein, Steven Geyer, Charles E. |
| description | Purpose
Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.
Methods
Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m
2
days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m
2
on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.
Results
399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77;
P
|
| doi_str_mv | 10.1007/s10549-007-9885-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69805338</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1599351891</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-4f9e04186c55a4122ef8d49677a385bfd9b7289cd1fc821429bbd623a6c0f24c3</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxiMEokvhAbggCwluAdtxYptbVfFnpUpc4BxNHLvrksTBk7TaviIvxax2RaVKXMbj8W9mPusriteCfxCc648oeK1sSWlpjalL_qTYiFpXpZZCPy02XDS6bAxvzooXiDecc6u5fV6cCSOMaazaFH8u2LwD9Gy73bIMU5_GeO975tI4Q46YJpYCG2CGJU6xY_OwInMwexcX6OLk2a3P-LgGQ6IYJ3aXRk8xLjsG_S1MjkZ32QMu1EC3zJYdLIwUsDmn6-wRiaClSyZmvV9H6D6xde5hoboPITpwe0Y6WRfTCPkXjYAJhj16fFk8CzCgf3U6z4ufXz7_uPxWXn3_ur28uCpdZe1SqmA9V8I0rq5BCSl9ML2yjdZQmboLve20NNb1IjgjhZK26_pGVtA4HqRy1Xnx_jiXJP9ePS7tGNH5YYDJpxXbxhpeV5Uh8O0j8CatmdRiK4VUykh9gMQRcjkhZh_aOUf62b4VvD3Y3B5tbg_pweaWU8-b0-C1G33_0HHylYB3JwDQwRDIWRfxHye55cIqTZw8ckhP07XPDwr_v_0vkeLEVw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>212448278</pqid></control><display><type>article</type><title>A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Cameron, David ; Casey, Michelle ; Press, Michael ; Lindquist, Deborah ; Pienkowski, Tadeusz ; Romieu, C. Gilles ; Chan, Stephen ; Jagiello-Gruszfeld, Agnieszka ; Kaufman, Bella ; Crown, John ; Chan, Arlene ; Campone, Mario ; Viens, Patrice ; Davidson, Neville ; Gorbounova, Vera ; Raats, Johannes Isaac ; Skarlos, Dimosthenis ; Newstat, Beth ; Roychowdhury, Debasish ; Paoletti, Paolo ; Oliva, Cristina ; Rubin, Stephen ; Stein, Steven ; Geyer, Charles E.</creator><creatorcontrib>Cameron, David ; Casey, Michelle ; Press, Michael ; Lindquist, Deborah ; Pienkowski, Tadeusz ; Romieu, C. Gilles ; Chan, Stephen ; Jagiello-Gruszfeld, Agnieszka ; Kaufman, Bella ; Crown, John ; Chan, Arlene ; Campone, Mario ; Viens, Patrice ; Davidson, Neville ; Gorbounova, Vera ; Raats, Johannes Isaac ; Skarlos, Dimosthenis ; Newstat, Beth ; Roychowdhury, Debasish ; Paoletti, Paolo ; Oliva, Cristina ; Rubin, Stephen ; Stein, Steven ; Geyer, Charles E.</creatorcontrib><description>Purpose
Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.
Methods
Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m
2
days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m
2
on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.
Results
399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77;
P
< 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55–1.12,
P
= 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13,
P
= 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib.
Conclusion
The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-007-9885-0</identifier><identifier>PMID: 18188694</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject><![CDATA[Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor ; Breast cancer ; Breast Neoplasms - drug therapy ; Cancer research ; Cancer therapies ; Capecitabine ; Clinical Trial ; Clinical trials ; Comparative studies ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Disease Progression ; Drug therapy ; Female ; Fluorouracil - administration & dosage ; Fluorouracil - analogs & derivatives ; Humans ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Metastasis ; Oncology ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Quinazolines - administration & dosage ; Trastuzumab]]></subject><ispartof>Breast cancer research and treatment, 2008-12, Vol.112 (3), p.533-543</ispartof><rights>Springer Science+Business Media, LLC. 2008</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-4f9e04186c55a4122ef8d49677a385bfd9b7289cd1fc821429bbd623a6c0f24c3</citedby><cites>FETCH-LOGICAL-c399t-4f9e04186c55a4122ef8d49677a385bfd9b7289cd1fc821429bbd623a6c0f24c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-007-9885-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-007-9885-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20901947$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18188694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cameron, David</creatorcontrib><creatorcontrib>Casey, Michelle</creatorcontrib><creatorcontrib>Press, Michael</creatorcontrib><creatorcontrib>Lindquist, Deborah</creatorcontrib><creatorcontrib>Pienkowski, Tadeusz</creatorcontrib><creatorcontrib>Romieu, C. Gilles</creatorcontrib><creatorcontrib>Chan, Stephen</creatorcontrib><creatorcontrib>Jagiello-Gruszfeld, Agnieszka</creatorcontrib><creatorcontrib>Kaufman, Bella</creatorcontrib><creatorcontrib>Crown, John</creatorcontrib><creatorcontrib>Chan, Arlene</creatorcontrib><creatorcontrib>Campone, Mario</creatorcontrib><creatorcontrib>Viens, Patrice</creatorcontrib><creatorcontrib>Davidson, Neville</creatorcontrib><creatorcontrib>Gorbounova, Vera</creatorcontrib><creatorcontrib>Raats, Johannes Isaac</creatorcontrib><creatorcontrib>Skarlos, Dimosthenis</creatorcontrib><creatorcontrib>Newstat, Beth</creatorcontrib><creatorcontrib>Roychowdhury, Debasish</creatorcontrib><creatorcontrib>Paoletti, Paolo</creatorcontrib><creatorcontrib>Oliva, Cristina</creatorcontrib><creatorcontrib>Rubin, Stephen</creatorcontrib><creatorcontrib>Stein, Steven</creatorcontrib><creatorcontrib>Geyer, Charles E.</creatorcontrib><title>A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.
Methods
Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m
2
days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m
2
on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.
Results
399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77;
P
< 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55–1.12,
P
= 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13,
P
= 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib.
Conclusion
The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Capecitabine</subject><subject>Clinical Trial</subject><subject>Clinical trials</subject><subject>Comparative studies</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Disease Progression</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - analogs & derivatives</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Quinazolines - administration & dosage</subject><subject>Trastuzumab</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc9u1DAQxiMEokvhAbggCwluAdtxYptbVfFnpUpc4BxNHLvrksTBk7TaviIvxax2RaVKXMbj8W9mPusriteCfxCc648oeK1sSWlpjalL_qTYiFpXpZZCPy02XDS6bAxvzooXiDecc6u5fV6cCSOMaazaFH8u2LwD9Gy73bIMU5_GeO975tI4Q46YJpYCG2CGJU6xY_OwInMwexcX6OLk2a3P-LgGQ6IYJ3aXRk8xLjsG_S1MjkZ32QMu1EC3zJYdLIwUsDmn6-wRiaClSyZmvV9H6D6xde5hoboPITpwe0Y6WRfTCPkXjYAJhj16fFk8CzCgf3U6z4ufXz7_uPxWXn3_ur28uCpdZe1SqmA9V8I0rq5BCSl9ML2yjdZQmboLve20NNb1IjgjhZK26_pGVtA4HqRy1Xnx_jiXJP9ePS7tGNH5YYDJpxXbxhpeV5Uh8O0j8CatmdRiK4VUykh9gMQRcjkhZh_aOUf62b4VvD3Y3B5tbg_pweaWU8-b0-C1G33_0HHylYB3JwDQwRDIWRfxHye55cIqTZw8ckhP07XPDwr_v_0vkeLEVw</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Cameron, David</creator><creator>Casey, Michelle</creator><creator>Press, Michael</creator><creator>Lindquist, Deborah</creator><creator>Pienkowski, Tadeusz</creator><creator>Romieu, C. Gilles</creator><creator>Chan, Stephen</creator><creator>Jagiello-Gruszfeld, Agnieszka</creator><creator>Kaufman, Bella</creator><creator>Crown, John</creator><creator>Chan, Arlene</creator><creator>Campone, Mario</creator><creator>Viens, Patrice</creator><creator>Davidson, Neville</creator><creator>Gorbounova, Vera</creator><creator>Raats, Johannes Isaac</creator><creator>Skarlos, Dimosthenis</creator><creator>Newstat, Beth</creator><creator>Roychowdhury, Debasish</creator><creator>Paoletti, Paolo</creator><creator>Oliva, Cristina</creator><creator>Rubin, Stephen</creator><creator>Stein, Steven</creator><creator>Geyer, Charles E.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses</title><author>Cameron, David ; Casey, Michelle ; Press, Michael ; Lindquist, Deborah ; Pienkowski, Tadeusz ; Romieu, C. Gilles ; Chan, Stephen ; Jagiello-Gruszfeld, Agnieszka ; Kaufman, Bella ; Crown, John ; Chan, Arlene ; Campone, Mario ; Viens, Patrice ; Davidson, Neville ; Gorbounova, Vera ; Raats, Johannes Isaac ; Skarlos, Dimosthenis ; Newstat, Beth ; Roychowdhury, Debasish ; Paoletti, Paolo ; Oliva, Cristina ; Rubin, Stephen ; Stein, Steven ; Geyer, Charles E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-4f9e04186c55a4122ef8d49677a385bfd9b7289cd1fc821429bbd623a6c0f24c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Capecitabine</topic><topic>Clinical Trial</topic><topic>Clinical trials</topic><topic>Comparative studies</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Disease Progression</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - analogs & derivatives</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Oncology</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Quinazolines - administration & dosage</topic><topic>Trastuzumab</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cameron, David</creatorcontrib><creatorcontrib>Casey, Michelle</creatorcontrib><creatorcontrib>Press, Michael</creatorcontrib><creatorcontrib>Lindquist, Deborah</creatorcontrib><creatorcontrib>Pienkowski, Tadeusz</creatorcontrib><creatorcontrib>Romieu, C. Gilles</creatorcontrib><creatorcontrib>Chan, Stephen</creatorcontrib><creatorcontrib>Jagiello-Gruszfeld, Agnieszka</creatorcontrib><creatorcontrib>Kaufman, Bella</creatorcontrib><creatorcontrib>Crown, John</creatorcontrib><creatorcontrib>Chan, Arlene</creatorcontrib><creatorcontrib>Campone, Mario</creatorcontrib><creatorcontrib>Viens, Patrice</creatorcontrib><creatorcontrib>Davidson, Neville</creatorcontrib><creatorcontrib>Gorbounova, Vera</creatorcontrib><creatorcontrib>Raats, Johannes Isaac</creatorcontrib><creatorcontrib>Skarlos, Dimosthenis</creatorcontrib><creatorcontrib>Newstat, Beth</creatorcontrib><creatorcontrib>Roychowdhury, Debasish</creatorcontrib><creatorcontrib>Paoletti, Paolo</creatorcontrib><creatorcontrib>Oliva, Cristina</creatorcontrib><creatorcontrib>Rubin, Stephen</creatorcontrib><creatorcontrib>Stein, Steven</creatorcontrib><creatorcontrib>Geyer, Charles E.</creatorcontrib><collection>Pascal-Francis</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>Oncogenes and Growth Factors 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>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cameron, David</au><au>Casey, Michelle</au><au>Press, Michael</au><au>Lindquist, Deborah</au><au>Pienkowski, Tadeusz</au><au>Romieu, C. Gilles</au><au>Chan, Stephen</au><au>Jagiello-Gruszfeld, Agnieszka</au><au>Kaufman, Bella</au><au>Crown, John</au><au>Chan, Arlene</au><au>Campone, Mario</au><au>Viens, Patrice</au><au>Davidson, Neville</au><au>Gorbounova, Vera</au><au>Raats, Johannes Isaac</au><au>Skarlos, Dimosthenis</au><au>Newstat, Beth</au><au>Roychowdhury, Debasish</au><au>Paoletti, Paolo</au><au>Oliva, Cristina</au><au>Rubin, Stephen</au><au>Stein, Steven</au><au>Geyer, Charles E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>112</volume><issue>3</issue><spage>533</spage><epage>543</epage><pages>533-543</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>Purpose
Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.
Methods
Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m
2
days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m
2
on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.
Results
399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77;
P
< 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55–1.12,
P
= 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13,
P
= 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib.
Conclusion
The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>18188694</pmid><doi>10.1007/s10549-007-9885-0</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2008-12, Vol.112 (3), p.533-543 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69805338 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adult Aged Aged, 80 and over Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor Breast cancer Breast Neoplasms - drug therapy Cancer research Cancer therapies Capecitabine Clinical Trial Clinical trials Comparative studies Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Disease Progression Drug therapy Female Fluorouracil - administration & dosage Fluorouracil - analogs & derivatives Humans Medicine Medicine & Public Health Middle Aged Neoplasm Metastasis Oncology Protein-Tyrosine Kinases - antagonists & inhibitors Quinazolines - administration & dosage Trastuzumab |
| title | A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T13%3A54%3A52IST&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=A%20phase%20III%20randomized%20comparison%20of%20lapatinib%20plus%20capecitabine%20versus%20capecitabine%20alone%20in%20women%20with%20advanced%20breast%20cancer%20that%20has%20progressed%20on%20trastuzumab:%20updated%20efficacy%20and%20biomarker%20analyses&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Cameron,%20David&rft.date=2008-12-01&rft.volume=112&rft.issue=3&rft.spage=533&rft.epage=543&rft.pages=533-543&rft.issn=0167-6806&rft.eissn=1573-7217&rft.coden=BCTRD6&rft_id=info:doi/10.1007/s10549-007-9885-0&rft_dat=%3Cproquest_cross%3E1599351891%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=212448278&rft_id=info:pmid/18188694&rfr_iscdi=true |