Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors
Summary Background : To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. Methods : Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study...
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| Veröffentlicht in: | Investigational new drugs 2012-04, Vol.30 (2), p.695-701 |
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| creator | Galsky, Matthew D. Von Hoff, Daniel D. Neubauer, Marcus Anderson, Thomas Fleming, Mark Nagarwala, Yasir Mahoney, Janine M. Midwinter, Dawn Vocila, Linda Zaks, Tal Z. |
| description | Summary
Background
: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.
Methods
: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.
Results
: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.
Conclusions
: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in “oncogene addiction”. |
| doi_str_mv | 10.1007/s10637-010-9541-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1112133426</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2789235501</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-6ec03d3c601d3f1bf10289cc9b34cb2bbadf69383a770e247c01c699caf5118a3</originalsourceid><addsrcrecordid>eNp1kM9rHCEUx6WkNNu0f0AvRcg1pu-Ns7pzDCFtCoFCSc_iqLMxzOhEHcL22L-8LpuEXHLxie_7Az-EfEE4RwD5LSMILhkgsG7dIoN3ZIVryRmIVhyRFaCQTHSdPCYfc74HAN7J9gM5bmCzlihhRf7d6rR1heXZGT94c0bvfC5xjNsd88G62dUjlDOadLBx8n-dpdZnE0PxYdHFx0BzWeyOxoGOeq4vwffUB7q_Vmemj77c0eur3w3T0zzWkhqR4-gtLcsUU_5E3g96zO7z0zwhf75f3V5es5tfP35eXtwwwyUWJpwBbrkRgJYP2A8IzaYzput5a_qm77UdRMc3XEsJrmmlATT180YPa8SN5ifk9JA7p_iwuFzUfVxSqJUKERvkvG1EVeFBZVLMOblBzclPOu0UgtpTVwfqqlJXe-oKqufrU_LST86-OJ4xV0FzEOS6CluXXlW_mfofPvaPfw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1112133426</pqid></control><display><type>article</type><title>Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Galsky, Matthew D. ; Von Hoff, Daniel D. ; Neubauer, Marcus ; Anderson, Thomas ; Fleming, Mark ; Nagarwala, Yasir ; Mahoney, Janine M. ; Midwinter, Dawn ; Vocila, Linda ; Zaks, Tal Z.</creator><creatorcontrib>Galsky, Matthew D. ; Von Hoff, Daniel D. ; Neubauer, Marcus ; Anderson, Thomas ; Fleming, Mark ; Nagarwala, Yasir ; Mahoney, Janine M. ; Midwinter, Dawn ; Vocila, Linda ; Zaks, Tal Z.</creatorcontrib><description>Summary
Background
: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.
Methods
: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.
Results
: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.
Conclusions
: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in “oncogene addiction”.</description><identifier>ISSN: 0167-6997</identifier><identifier>EISSN: 1573-0646</identifier><identifier>DOI: 10.1007/s10637-010-9541-0</identifier><identifier>PMID: 20857170</identifier><identifier>CODEN: INNDDK</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject><![CDATA[Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - administration & dosage ; Biomarkers, Tumor - antagonists & inhibitors ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Bladder ; Bladder cancer ; Cancer therapies ; Clinical trials ; Creatinine ; Disease-Free Survival ; Double-Blind Method ; Drug Administration Schedule ; Drugs ; Esophagus ; Female ; Gene Amplification ; Histology ; Humans ; In Situ Hybridization, Fluorescence ; Inhibitor drugs ; Kinases ; Laboratories ; Male ; Medicine ; Medicine & Public Health ; Metastasis ; Middle Aged ; Molecular Targeted Therapy ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - genetics ; Neoplasms - pathology ; Oncology ; Ovarian cancer ; Patient Selection ; Patients ; Pharmacology ; Pharmacology/Toxicology ; Phase II Studies ; Precision Medicine ; Protein Kinase Inhibitors - administration & dosage ; Quinazolines - administration & dosage ; Receptor, ErbB-2 - antagonists & inhibitors ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; Response rates ; Studies ; Time Factors ; Treatment Outcome ; Tumors ; United States]]></subject><ispartof>Investigational new drugs, 2012-04, Vol.30 (2), p.695-701</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><rights>Springer Science+Business Media, LLC 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-6ec03d3c601d3f1bf10289cc9b34cb2bbadf69383a770e247c01c699caf5118a3</citedby><cites>FETCH-LOGICAL-c371t-6ec03d3c601d3f1bf10289cc9b34cb2bbadf69383a770e247c01c699caf5118a3</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/s10637-010-9541-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10637-010-9541-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20857170$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galsky, Matthew D.</creatorcontrib><creatorcontrib>Von Hoff, Daniel D.</creatorcontrib><creatorcontrib>Neubauer, Marcus</creatorcontrib><creatorcontrib>Anderson, Thomas</creatorcontrib><creatorcontrib>Fleming, Mark</creatorcontrib><creatorcontrib>Nagarwala, Yasir</creatorcontrib><creatorcontrib>Mahoney, Janine M.</creatorcontrib><creatorcontrib>Midwinter, Dawn</creatorcontrib><creatorcontrib>Vocila, Linda</creatorcontrib><creatorcontrib>Zaks, Tal Z.</creatorcontrib><title>Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors</title><title>Investigational new drugs</title><addtitle>Invest New Drugs</addtitle><addtitle>Invest New Drugs</addtitle><description>Summary
Background
: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.
Methods
: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.
Results
: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.
Conclusions
: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in “oncogene addiction”.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Biomarkers, Tumor - antagonists & inhibitors</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Cancer therapies</subject><subject>Clinical trials</subject><subject>Creatinine</subject><subject>Disease-Free Survival</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Drugs</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gene Amplification</subject><subject>Histology</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Inhibitor drugs</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Targeted Therapy</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Patient Selection</subject><subject>Patients</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Phase II Studies</subject><subject>Precision Medicine</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Quinazolines - administration & dosage</subject><subject>Receptor, ErbB-2 - antagonists & inhibitors</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Response rates</subject><subject>Studies</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>United States</subject><issn>0167-6997</issn><issn>1573-0646</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kM9rHCEUx6WkNNu0f0AvRcg1pu-Ns7pzDCFtCoFCSc_iqLMxzOhEHcL22L-8LpuEXHLxie_7Az-EfEE4RwD5LSMILhkgsG7dIoN3ZIVryRmIVhyRFaCQTHSdPCYfc74HAN7J9gM5bmCzlihhRf7d6rR1heXZGT94c0bvfC5xjNsd88G62dUjlDOadLBx8n-dpdZnE0PxYdHFx0BzWeyOxoGOeq4vwffUB7q_Vmemj77c0eur3w3T0zzWkhqR4-gtLcsUU_5E3g96zO7z0zwhf75f3V5es5tfP35eXtwwwyUWJpwBbrkRgJYP2A8IzaYzput5a_qm77UdRMc3XEsJrmmlATT180YPa8SN5ifk9JA7p_iwuFzUfVxSqJUKERvkvG1EVeFBZVLMOblBzclPOu0UgtpTVwfqqlJXe-oKqufrU_LST86-OJ4xV0FzEOS6CluXXlW_mfofPvaPfw</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Galsky, Matthew D.</creator><creator>Von Hoff, Daniel D.</creator><creator>Neubauer, Marcus</creator><creator>Anderson, Thomas</creator><creator>Fleming, Mark</creator><creator>Nagarwala, Yasir</creator><creator>Mahoney, Janine M.</creator><creator>Midwinter, Dawn</creator><creator>Vocila, Linda</creator><creator>Zaks, Tal Z.</creator><general>Springer US</general><general>Springer Nature B.V</general><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>7QO</scope><scope>7RV</scope><scope>7WY</scope><scope>7WZ</scope><scope>7X7</scope><scope>7XB</scope><scope>87Z</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FL</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FRNLG</scope><scope>FYUFA</scope><scope>F~G</scope><scope>GHDGH</scope><scope>K60</scope><scope>K6~</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>L.-</scope><scope>M0C</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20120401</creationdate><title>Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors</title><author>Galsky, Matthew D. ; Von Hoff, Daniel D. ; Neubauer, Marcus ; Anderson, Thomas ; Fleming, Mark ; Nagarwala, Yasir ; Mahoney, Janine M. ; Midwinter, Dawn ; Vocila, Linda ; Zaks, Tal Z.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-6ec03d3c601d3f1bf10289cc9b34cb2bbadf69383a770e247c01c699caf5118a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Biomarkers, Tumor - antagonists & inhibitors</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bladder</topic><topic>Bladder cancer</topic><topic>Cancer therapies</topic><topic>Clinical trials</topic><topic>Creatinine</topic><topic>Disease-Free Survival</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Drugs</topic><topic>Esophagus</topic><topic>Female</topic><topic>Gene Amplification</topic><topic>Histology</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Inhibitor drugs</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Targeted Therapy</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Patient Selection</topic><topic>Patients</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Phase II Studies</topic><topic>Precision Medicine</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Quinazolines - administration & dosage</topic><topic>Receptor, ErbB-2 - antagonists & inhibitors</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Response rates</topic><topic>Studies</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Galsky, Matthew D.</creatorcontrib><creatorcontrib>Von Hoff, Daniel D.</creatorcontrib><creatorcontrib>Neubauer, Marcus</creatorcontrib><creatorcontrib>Anderson, Thomas</creatorcontrib><creatorcontrib>Fleming, Mark</creatorcontrib><creatorcontrib>Nagarwala, Yasir</creatorcontrib><creatorcontrib>Mahoney, Janine M.</creatorcontrib><creatorcontrib>Midwinter, Dawn</creatorcontrib><creatorcontrib>Vocila, Linda</creatorcontrib><creatorcontrib>Zaks, Tal Z.</creatorcontrib><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>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Access via ABI/INFORM (ProQuest)</collection><collection>ABI/INFORM Global (PDF only)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ABI/INFORM Global (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ABI/INFORM Collection (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>Business Premium Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Business Premium Collection (Alumni)</collection><collection>Health Research Premium Collection</collection><collection>ABI/INFORM Global (Corporate)</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Business Collection (Alumni Edition)</collection><collection>ProQuest Business Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ABI/INFORM Professional Advanced</collection><collection>ABI/INFORM Global</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Business</collection><collection>ProQuest One Business (Alumni)</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 Basic</collection><jtitle>Investigational new drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Galsky, Matthew D.</au><au>Von Hoff, Daniel D.</au><au>Neubauer, Marcus</au><au>Anderson, Thomas</au><au>Fleming, Mark</au><au>Nagarwala, Yasir</au><au>Mahoney, Janine M.</au><au>Midwinter, Dawn</au><au>Vocila, Linda</au><au>Zaks, Tal Z.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors</atitle><jtitle>Investigational new drugs</jtitle><stitle>Invest New Drugs</stitle><addtitle>Invest New Drugs</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>30</volume><issue>2</issue><spage>695</spage><epage>701</epage><pages>695-701</pages><issn>0167-6997</issn><eissn>1573-0646</eissn><coden>INNDDK</coden><abstract>Summary
Background
: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.
Methods
: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.
Results
: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.
Conclusions
: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in “oncogene addiction”.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>20857170</pmid><doi>10.1007/s10637-010-9541-0</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Investigational new drugs, 2012-04, Vol.30 (2), p.695-701 |
| issn | 0167-6997 1573-0646 |
| language | eng |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - administration & dosage Biomarkers, Tumor - antagonists & inhibitors Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Bladder Bladder cancer Cancer therapies Clinical trials Creatinine Disease-Free Survival Double-Blind Method Drug Administration Schedule Drugs Esophagus Female Gene Amplification Histology Humans In Situ Hybridization, Fluorescence Inhibitor drugs Kinases Laboratories Male Medicine Medicine & Public Health Metastasis Middle Aged Molecular Targeted Therapy Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - genetics Neoplasms - pathology Oncology Ovarian cancer Patient Selection Patients Pharmacology Pharmacology/Toxicology Phase II Studies Precision Medicine Protein Kinase Inhibitors - administration & dosage Quinazolines - administration & dosage Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Response rates Studies Time Factors Treatment Outcome Tumors United States |
| title | Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors |
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