Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer
Background Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m 2 paclitaxel), has been shown to be effe...
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| Veröffentlicht in: | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2018-03, Vol.21 (2), p.276-284 |
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| creator | Kim, Tae You Yen, Chia-Jui Al-Batran, Salah-Eddin Ferry, David Gao, Ling Hsu, Yanzhi Cheng, Rebecca Orlando, Mauro Ohtsu, Atsushi |
| description | Background
Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m
2
paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure–response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial.
Methods
Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (
C
min,ss
) using a nonlinear mixed-effect modeling approach. Kaplan–Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (
C
min,ss
) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively.
Results
Two hundred and twenty-two East Asian patients were included in this exposure–response analysis. Higher ramucirumab
C
min,ss
was associated with longer overall survival (
p
= 0.0115) and progression-free survival (
p
= 0.0179) in this patient cohort. Patients with higher ramucirumab
C
min,ss
(≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension.
Conclusions
This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure–response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer. |
| doi_str_mv | 10.1007/s10120-017-0737-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2009483395</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2009483395</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-d8952ddb71c545ae93d2c0b7a387d86ee4b74463ee68b50d301fb97ad7147d0e3</originalsourceid><addsrcrecordid>eNp1kc1u1DAUhS0Eoj_wAGyQJdZpr38SJ-yGavojVVRCrVhajn1TXE3sYCdS2xXvwJK340nwaFpYsbGvrs_5juRDyDsGRwxAHWcGjEMFTFWghKr4C7LPpGgqIaB--Tzzju2Rg5zvAFjdseY12eNtI6SS7T75tb6fYl4S_v7xM2GeYshIE27M7Mv4zU80DjSZcbE-LaPpqQ90bfJMV9mbQKeiwzBnOqQ40i-ri8-frr5-pKZYgoujf0RH7cYHb82GzsmXswAy2hhcVfZYlmjmsTC2QbeFnLyl1gSL6Q15NZhNxrdP9yG5OV1fn5xXl1dnFyery8rKppkr13Y1d65XzNayNtgJxy30yohWubZBlL2SshGITdvX4ASwoe-UcYpJ5QDFIfmw404pfl8wz_ouLimUSM0BOtkK0dVFxXYqm2LOCQc9JT-a9KAZ6G0deleHLnXobR2aF8_7J_LSj-j-Op7_vwj4TpDLU7jF9C_6_9Q_LyGYtA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2009483395</pqid></control><display><type>article</type><title>Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Kim, Tae You ; Yen, Chia-Jui ; Al-Batran, Salah-Eddin ; Ferry, David ; Gao, Ling ; Hsu, Yanzhi ; Cheng, Rebecca ; Orlando, Mauro ; Ohtsu, Atsushi</creator><creatorcontrib>Kim, Tae You ; Yen, Chia-Jui ; Al-Batran, Salah-Eddin ; Ferry, David ; Gao, Ling ; Hsu, Yanzhi ; Cheng, Rebecca ; Orlando, Mauro ; Ohtsu, Atsushi</creatorcontrib><description>Background
Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m
2
paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure–response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial.
Methods
Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (
C
min,ss
) using a nonlinear mixed-effect modeling approach. Kaplan–Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (
C
min,ss
) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively.
Results
Two hundred and twenty-two East Asian patients were included in this exposure–response analysis. Higher ramucirumab
C
min,ss
was associated with longer overall survival (
p
= 0.0115) and progression-free survival (
p
= 0.0179) in this patient cohort. Patients with higher ramucirumab
C
min,ss
(≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension.
Conclusions
This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure–response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.</description><identifier>ISSN: 1436-3291</identifier><identifier>EISSN: 1436-3305</identifier><identifier>DOI: 10.1007/s10120-017-0737-2</identifier><identifier>PMID: 28634748</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Abdominal Surgery ; Adenocarcinoma ; Adenocarcinoma - drug therapy ; Adenocarcinoma - mortality ; Adult ; Aged ; Antibodies, Monoclonal - pharmacokinetics ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological - pharmacokinetics ; Antineoplastic Agents, Immunological - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Asian People ; Cancer Research ; Clinical trials ; Disease-Free Survival ; Female ; Gastric cancer ; Gastroenterology ; Humans ; Immunoglobulin G ; Immunotherapy ; Kaplan-Meier Estimate ; Leukopenia ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Monoclonal antibodies ; Neutropenia ; Oncology ; Original Article ; Paclitaxel ; Paclitaxel - therapeutic use ; Patients ; Proportional Hazards Models ; Ramucirumab ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - mortality ; Surgical Oncology ; Survival ; Targeted cancer therapy ; Vascular endothelial growth factor ; Vascular endothelial growth factor receptors</subject><ispartof>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018-03, Vol.21 (2), p.276-284</ispartof><rights>The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2017</rights><rights>Gastric Cancer is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-d8952ddb71c545ae93d2c0b7a387d86ee4b74463ee68b50d301fb97ad7147d0e3</citedby><cites>FETCH-LOGICAL-c466t-d8952ddb71c545ae93d2c0b7a387d86ee4b74463ee68b50d301fb97ad7147d0e3</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/s10120-017-0737-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10120-017-0737-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28634748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Tae You</creatorcontrib><creatorcontrib>Yen, Chia-Jui</creatorcontrib><creatorcontrib>Al-Batran, Salah-Eddin</creatorcontrib><creatorcontrib>Ferry, David</creatorcontrib><creatorcontrib>Gao, Ling</creatorcontrib><creatorcontrib>Hsu, Yanzhi</creatorcontrib><creatorcontrib>Cheng, Rebecca</creatorcontrib><creatorcontrib>Orlando, Mauro</creatorcontrib><creatorcontrib>Ohtsu, Atsushi</creatorcontrib><title>Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer</title><title>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</title><addtitle>Gastric Cancer</addtitle><addtitle>Gastric Cancer</addtitle><description>Background
Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m
2
paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure–response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial.
Methods
Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (
C
min,ss
) using a nonlinear mixed-effect modeling approach. Kaplan–Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (
C
min,ss
) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively.
Results
Two hundred and twenty-two East Asian patients were included in this exposure–response analysis. Higher ramucirumab
C
min,ss
was associated with longer overall survival (
p
= 0.0115) and progression-free survival (
p
= 0.0179) in this patient cohort. Patients with higher ramucirumab
C
min,ss
(≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension.
Conclusions
This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure–response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.</description><subject>Abdominal Surgery</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - mortality</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal - pharmacokinetics</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Agents, Immunological - pharmacokinetics</subject><subject>Antineoplastic Agents, Immunological - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Asian People</subject><subject>Cancer Research</subject><subject>Clinical trials</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gastroenterology</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukopenia</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Neutropenia</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Paclitaxel</subject><subject>Paclitaxel - therapeutic use</subject><subject>Patients</subject><subject>Proportional Hazards Models</subject><subject>Ramucirumab</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - mortality</subject><subject>Surgical Oncology</subject><subject>Survival</subject><subject>Targeted cancer therapy</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular endothelial growth factor receptors</subject><issn>1436-3291</issn><issn>1436-3305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc1u1DAUhS0Eoj_wAGyQJdZpr38SJ-yGavojVVRCrVhajn1TXE3sYCdS2xXvwJK340nwaFpYsbGvrs_5juRDyDsGRwxAHWcGjEMFTFWghKr4C7LPpGgqIaB--Tzzju2Rg5zvAFjdseY12eNtI6SS7T75tb6fYl4S_v7xM2GeYshIE27M7Mv4zU80DjSZcbE-LaPpqQ90bfJMV9mbQKeiwzBnOqQ40i-ri8-frr5-pKZYgoujf0RH7cYHb82GzsmXswAy2hhcVfZYlmjmsTC2QbeFnLyl1gSL6Q15NZhNxrdP9yG5OV1fn5xXl1dnFyery8rKppkr13Y1d65XzNayNtgJxy30yohWubZBlL2SshGITdvX4ASwoe-UcYpJ5QDFIfmw404pfl8wz_ouLimUSM0BOtkK0dVFxXYqm2LOCQc9JT-a9KAZ6G0deleHLnXobR2aF8_7J_LSj-j-Op7_vwj4TpDLU7jF9C_6_9Q_LyGYtA</recordid><startdate>20180301</startdate><enddate>20180301</enddate><creator>Kim, Tae You</creator><creator>Yen, Chia-Jui</creator><creator>Al-Batran, Salah-Eddin</creator><creator>Ferry, David</creator><creator>Gao, Ling</creator><creator>Hsu, Yanzhi</creator><creator>Cheng, Rebecca</creator><creator>Orlando, Mauro</creator><creator>Ohtsu, Atsushi</creator><general>Springer Japan</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>7T5</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>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20180301</creationdate><title>Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer</title><author>Kim, Tae You ; Yen, Chia-Jui ; Al-Batran, Salah-Eddin ; Ferry, David ; Gao, Ling ; Hsu, Yanzhi ; Cheng, Rebecca ; Orlando, Mauro ; Ohtsu, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-d8952ddb71c545ae93d2c0b7a387d86ee4b74463ee68b50d301fb97ad7147d0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Abdominal Surgery</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - mortality</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal - pharmacokinetics</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic Agents, Immunological - pharmacokinetics</topic><topic>Antineoplastic Agents, Immunological - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Asian People</topic><topic>Cancer Research</topic><topic>Clinical trials</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gastroenterology</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukopenia</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Neutropenia</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Paclitaxel</topic><topic>Paclitaxel - therapeutic use</topic><topic>Patients</topic><topic>Proportional Hazards Models</topic><topic>Ramucirumab</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - mortality</topic><topic>Surgical Oncology</topic><topic>Survival</topic><topic>Targeted cancer therapy</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular endothelial growth factor receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Tae You</creatorcontrib><creatorcontrib>Yen, Chia-Jui</creatorcontrib><creatorcontrib>Al-Batran, Salah-Eddin</creatorcontrib><creatorcontrib>Ferry, David</creatorcontrib><creatorcontrib>Gao, Ling</creatorcontrib><creatorcontrib>Hsu, Yanzhi</creatorcontrib><creatorcontrib>Cheng, Rebecca</creatorcontrib><creatorcontrib>Orlando, Mauro</creatorcontrib><creatorcontrib>Ohtsu, Atsushi</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>Immunology 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Tae You</au><au>Yen, Chia-Jui</au><au>Al-Batran, Salah-Eddin</au><au>Ferry, David</au><au>Gao, Ling</au><au>Hsu, Yanzhi</au><au>Cheng, Rebecca</au><au>Orlando, Mauro</au><au>Ohtsu, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer</atitle><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle><stitle>Gastric Cancer</stitle><addtitle>Gastric Cancer</addtitle><date>2018-03-01</date><risdate>2018</risdate><volume>21</volume><issue>2</issue><spage>276</spage><epage>284</epage><pages>276-284</pages><issn>1436-3291</issn><eissn>1436-3305</eissn><abstract>Background
Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m
2
paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure–response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial.
Methods
Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (
C
min,ss
) using a nonlinear mixed-effect modeling approach. Kaplan–Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (
C
min,ss
) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively.
Results
Two hundred and twenty-two East Asian patients were included in this exposure–response analysis. Higher ramucirumab
C
min,ss
was associated with longer overall survival (
p
= 0.0115) and progression-free survival (
p
= 0.0179) in this patient cohort. Patients with higher ramucirumab
C
min,ss
(≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension.
Conclusions
This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure–response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>28634748</pmid><doi>10.1007/s10120-017-0737-2</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1436-3291 |
| ispartof | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018-03, Vol.21 (2), p.276-284 |
| issn | 1436-3291 1436-3305 |
| language | eng |
| recordid | cdi_proquest_journals_2009483395 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Abdominal Surgery Adenocarcinoma Adenocarcinoma - drug therapy Adenocarcinoma - mortality Adult Aged Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized Antineoplastic Agents, Immunological - pharmacokinetics Antineoplastic Agents, Immunological - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Asian People Cancer Research Clinical trials Disease-Free Survival Female Gastric cancer Gastroenterology Humans Immunoglobulin G Immunotherapy Kaplan-Meier Estimate Leukopenia Male Medicine Medicine & Public Health Middle Aged Monoclonal antibodies Neutropenia Oncology Original Article Paclitaxel Paclitaxel - therapeutic use Patients Proportional Hazards Models Ramucirumab Stomach Neoplasms - drug therapy Stomach Neoplasms - mortality Surgical Oncology Survival Targeted cancer therapy Vascular endothelial growth factor Vascular endothelial growth factor receptors |
| title | Exposure–response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer |
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