Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-es...
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| Veröffentlicht in: | The lancet oncology 2023-11, Vol.24 (11), p.1181-1195 |
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| creator | Oh, Do-Youn Yañez, Patricio Bai, Yuxian Ryu, Min-Hee Rivera, Fernando Alves, Gustavo Vasconcelos Garrido, Marcelo Shiu, Kai-Keen Çil, Timuçin Pan, Hongming Wainberg, Zev A O'Connor, Juan Manuel Cundom, Juan Ng, Weng Peressoni, Mauricio Andrade, Carlos Alves, Gustavo Vianna, Karina Monteiro, Maria Marcela Tan, Ann Asselah, Jamil Mahave, Mauricio Salman, Pamela Liu, Tianshu Lin, Xiaoyan Li, Wei Qu, Yanli Chen, Ping Liang, Xinjun Zhao, Qun Yin, Xianli Li, Junhe Guerrero, Alvaro Rubiano, Juan Gonzalez Herrera, Ileana Melichar, Bohuslav Buchler, Tomas Svoboda, Tomas Vrana, David Cvek, Jakub Pfeiffer, Per Baeksgaard, Lene Yilmaz, Mette Boige, Valerie Lopez-Trabada, Daniel Hiret, Sandrine Arnold, Dirk Martens, Uwe Castro, Hugo Lopez, Karla Chivalan, Marco Chan, Wendy Horvath, Zsolt Lowery, Maeve Pelles Avraham, Sharon Di Bartolomeo, Maria Lonardi, Sara Yasui, Hisateru Shoji, Hirokazu Shibata, Nobuhiro Yamaguchi, Kensei Esaki, Taito Yabusaki, Hiroshi Tsuji, Akihito Kadowaki, Shigenori Martinez Rodriguez, Jorge Herrera Martinez, Marytere Balancan, Paola Castro Oliden, Victor Grados, Julio Hajac, Lukasz Rha, Sun Young Ryu, Min-Hee Oh, Do-Youn Orlova, Rashida Tjulandin, Sergey Chan, Sze Landers, Gregory Robertson, Barbara Ruff, Paul Rivera Herrero, Fernando Miranda Poma, Jesus Layos Romero, Laura Dosso, Sara De Yen, Chia-Jui Chen, Yen-Yang Oksuzoglu, Berna Hacibekiroglu, Ilhan Kolesnik, Oleksii Kryzhanivska, Anna Leshchenko, Lurii Ilin, Ievgen Voitko, Nataliia Roy, Rajarshi Shiu, Kai-Keen Overton, Lindsay Dunne, Richard Dayyani, Farshid Larson, Timothy Kochenderfer, Mark |
| description | PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1–5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1–14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.
Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR |
| doi_str_mv | 10.1016/S1470-2045(23)00515-6 |
| format | Article |
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Yañez, Patricio ; Bai, Yuxian ; Ryu, Min-Hee ; Rivera, Fernando ; Alves, Gustavo Vasconcelos ; Garrido, Marcelo ; Shiu, Kai-Keen ; Çil, Timuçin ; Pan, Hongming ; Wainberg, Zev A ; O'Connor, Juan Manuel ; Cundom, Juan ; Ng, Weng ; Peressoni, Mauricio ; Andrade, Carlos ; Alves, Gustavo ; Vianna, Karina ; Monteiro, Maria Marcela ; Tan, Ann ; Asselah, Jamil ; Mahave, Mauricio ; Salman, Pamela ; Liu, Tianshu ; Lin, Xiaoyan ; Li, Wei ; Qu, Yanli ; Chen, Ping ; Liang, Xinjun ; Zhao, Qun ; Yin, Xianli ; Li, Junhe ; Guerrero, Alvaro ; Rubiano, Juan ; Gonzalez Herrera, Ileana ; Melichar, Bohuslav ; Buchler, Tomas ; Svoboda, Tomas ; Vrana, David ; Cvek, Jakub ; Pfeiffer, Per ; Baeksgaard, Lene ; Yilmaz, Mette ; Boige, Valerie ; Lopez-Trabada, Daniel ; Hiret, Sandrine ; Arnold, Dirk ; Martens, Uwe ; Castro, Hugo ; Lopez, Karla ; Chivalan, Marco ; Chan, Wendy ; Horvath, Zsolt ; Lowery, Maeve ; Pelles Avraham, Sharon ; Di Bartolomeo, Maria ; Lonardi, Sara ; Yasui, Hisateru ; Shoji, Hirokazu ; Shibata, Nobuhiro ; Yamaguchi, Kensei ; Esaki, Taito ; Yabusaki, Hiroshi ; Tsuji, Akihito ; Kadowaki, Shigenori ; Martinez Rodriguez, Jorge ; Herrera Martinez, Marytere ; Balancan, Paola ; Castro Oliden, Victor ; Grados, Julio ; Hajac, Lukasz ; Rha, Sun Young ; Ryu, Min-Hee ; Oh, Do-Youn ; Orlova, Rashida ; Tjulandin, Sergey ; Chan, Sze ; Landers, Gregory ; Robertson, Barbara ; Ruff, Paul ; Rivera Herrero, Fernando ; Miranda Poma, Jesus ; Layos Romero, Laura ; Dosso, Sara De ; Yen, Chia-Jui ; Chen, Yen-Yang ; Oksuzoglu, Berna ; Hacibekiroglu, Ilhan ; Kolesnik, Oleksii ; Kryzhanivska, Anna ; Leshchenko, Lurii ; Ilin, Ievgen ; Voitko, Nataliia ; Roy, Rajarshi ; Shiu, Kai-Keen ; Overton, Lindsay ; Dunne, Richard ; Dayyani, Farshid ; Larson, Timothy ; Kochenderfer, Mark</creator><creatorcontrib>Oh, Do-Youn ; Yañez, Patricio ; Bai, Yuxian ; Ryu, Min-Hee ; Rivera, Fernando ; Alves, Gustavo Vasconcelos ; Garrido, Marcelo ; Shiu, Kai-Keen ; Çil, Timuçin ; Pan, Hongming ; Wainberg, Zev A ; O'Connor, Juan Manuel ; Cundom, Juan ; Ng, Weng ; Peressoni, Mauricio ; Andrade, Carlos ; Alves, Gustavo ; Vianna, Karina ; Monteiro, Maria Marcela ; Tan, Ann ; Asselah, Jamil ; Mahave, Mauricio ; Salman, Pamela ; Liu, Tianshu ; Lin, Xiaoyan ; Li, Wei ; Qu, Yanli ; Chen, Ping ; Liang, Xinjun ; Zhao, Qun ; Yin, Xianli ; Li, Junhe ; Guerrero, Alvaro ; Rubiano, Juan ; Gonzalez Herrera, Ileana ; Melichar, Bohuslav ; Buchler, Tomas ; Svoboda, Tomas ; Vrana, David ; Cvek, Jakub ; Pfeiffer, Per ; Baeksgaard, Lene ; Yilmaz, Mette ; Boige, Valerie ; Lopez-Trabada, Daniel ; Hiret, Sandrine ; Arnold, Dirk ; Martens, Uwe ; Castro, Hugo ; Lopez, Karla ; Chivalan, Marco ; Chan, Wendy ; Horvath, Zsolt ; Lowery, Maeve ; Pelles Avraham, Sharon ; Di Bartolomeo, Maria ; Lonardi, Sara ; Yasui, Hisateru ; Shoji, Hirokazu ; Shibata, Nobuhiro ; Yamaguchi, Kensei ; Esaki, Taito ; Yabusaki, Hiroshi ; Tsuji, Akihito ; Kadowaki, Shigenori ; Martinez Rodriguez, Jorge ; Herrera Martinez, Marytere ; Balancan, Paola ; Castro Oliden, Victor ; Grados, Julio ; Hajac, Lukasz ; Rha, Sun Young ; Ryu, Min-Hee ; Oh, Do-Youn ; Orlova, Rashida ; Tjulandin, Sergey ; Chan, Sze ; Landers, Gregory ; Robertson, Barbara ; Ruff, Paul ; Rivera Herrero, Fernando ; Miranda Poma, Jesus ; Layos Romero, Laura ; Dosso, Sara De ; Yen, Chia-Jui ; Chen, Yen-Yang ; Oksuzoglu, Berna ; Hacibekiroglu, Ilhan ; Kolesnik, Oleksii ; Kryzhanivska, Anna ; Leshchenko, Lurii ; Ilin, Ievgen ; Voitko, Nataliia ; Roy, Rajarshi ; Shiu, Kai-Keen ; Overton, Lindsay ; Dunne, Richard ; Dayyani, Farshid ; Larson, Timothy ; Kochenderfer, Mark ; KEYNOTE-859 investigators</creatorcontrib><description>PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1–5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1–14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.
Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0–38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9–14·0] vs 11·5 months [10·6–12·1]; hazard ratio [HR] 0·78 [95% CI 0·70–0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6–14·2] vs 11·4 months [10·5–12·0]; 0·74 [0·65–0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8–19·3] vs 11·8 months [10·3–12·7]; 0·65 [0·53–0·79]; p<0·0001). The most common grade 3–5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified.
Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
Merck Sharp and Dohme.</description><identifier>ISSN: 1470-2045</identifier><identifier>ISSN: 1474-5488</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(23)00515-6</identifier><identifier>PMID: 37875143</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>5-Fluorouracil ; Adenocarcinoma ; Adenocarcinoma - drug therapy ; Adverse events ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; B7-H1 Antigen ; Cancer therapies ; Chemotherapy ; Cisplatin ; Double-Blind Method ; Double-blind studies ; ErbB-2 protein ; Esophageal Neoplasms ; Esophagus ; Female ; Gastric cancer ; Hepatitis ; Humans ; Immunotherapy ; Intravenous administration ; Leukocytes (neutrophilic) ; Male ; Metastases ; Metastasis ; Monoclonal antibodies ; Oxaliplatin ; Patients ; PD-1 protein ; PD-L1 protein ; Pembrolizumab ; Placebos ; Safety ; Stomach Neoplasms - pathology ; Targeted cancer therapy ; Toxicity ; Tumors</subject><ispartof>The lancet oncology, 2023-11, Vol.24 (11), p.1181-1195</ispartof><rights>2023 Elsevier Ltd</rights><rights>Copyright © 2023 Elsevier Ltd. All rights reserved.</rights><rights>2023. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-642945c8ac2daead6b8c3035b9b2c75f738e7256adfd7056051d0f2529cbfab13</citedby><cites>FETCH-LOGICAL-c393t-642945c8ac2daead6b8c3035b9b2c75f738e7256adfd7056051d0f2529cbfab13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2884672579?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000,64390,64392,64394,72474</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37875143$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oh, Do-Youn</creatorcontrib><creatorcontrib>Yañez, Patricio</creatorcontrib><creatorcontrib>Bai, Yuxian</creatorcontrib><creatorcontrib>Ryu, Min-Hee</creatorcontrib><creatorcontrib>Rivera, Fernando</creatorcontrib><creatorcontrib>Alves, Gustavo Vasconcelos</creatorcontrib><creatorcontrib>Garrido, Marcelo</creatorcontrib><creatorcontrib>Shiu, Kai-Keen</creatorcontrib><creatorcontrib>Çil, Timuçin</creatorcontrib><creatorcontrib>Pan, Hongming</creatorcontrib><creatorcontrib>Wainberg, Zev A</creatorcontrib><creatorcontrib>O'Connor, Juan Manuel</creatorcontrib><creatorcontrib>Cundom, Juan</creatorcontrib><creatorcontrib>Ng, Weng</creatorcontrib><creatorcontrib>Peressoni, Mauricio</creatorcontrib><creatorcontrib>Andrade, Carlos</creatorcontrib><creatorcontrib>Alves, Gustavo</creatorcontrib><creatorcontrib>Vianna, Karina</creatorcontrib><creatorcontrib>Monteiro, Maria Marcela</creatorcontrib><creatorcontrib>Tan, Ann</creatorcontrib><creatorcontrib>Asselah, Jamil</creatorcontrib><creatorcontrib>Mahave, Mauricio</creatorcontrib><creatorcontrib>Salman, Pamela</creatorcontrib><creatorcontrib>Liu, Tianshu</creatorcontrib><creatorcontrib>Lin, Xiaoyan</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Qu, Yanli</creatorcontrib><creatorcontrib>Chen, Ping</creatorcontrib><creatorcontrib>Liang, Xinjun</creatorcontrib><creatorcontrib>Zhao, Qun</creatorcontrib><creatorcontrib>Yin, Xianli</creatorcontrib><creatorcontrib>Li, Junhe</creatorcontrib><creatorcontrib>Guerrero, Alvaro</creatorcontrib><creatorcontrib>Rubiano, Juan</creatorcontrib><creatorcontrib>Gonzalez Herrera, Ileana</creatorcontrib><creatorcontrib>Melichar, Bohuslav</creatorcontrib><creatorcontrib>Buchler, Tomas</creatorcontrib><creatorcontrib>Svoboda, Tomas</creatorcontrib><creatorcontrib>Vrana, David</creatorcontrib><creatorcontrib>Cvek, Jakub</creatorcontrib><creatorcontrib>Pfeiffer, Per</creatorcontrib><creatorcontrib>Baeksgaard, Lene</creatorcontrib><creatorcontrib>Yilmaz, Mette</creatorcontrib><creatorcontrib>Boige, Valerie</creatorcontrib><creatorcontrib>Lopez-Trabada, Daniel</creatorcontrib><creatorcontrib>Hiret, Sandrine</creatorcontrib><creatorcontrib>Arnold, Dirk</creatorcontrib><creatorcontrib>Martens, Uwe</creatorcontrib><creatorcontrib>Castro, Hugo</creatorcontrib><creatorcontrib>Lopez, Karla</creatorcontrib><creatorcontrib>Chivalan, Marco</creatorcontrib><creatorcontrib>Chan, Wendy</creatorcontrib><creatorcontrib>Horvath, Zsolt</creatorcontrib><creatorcontrib>Lowery, Maeve</creatorcontrib><creatorcontrib>Pelles Avraham, Sharon</creatorcontrib><creatorcontrib>Di Bartolomeo, Maria</creatorcontrib><creatorcontrib>Lonardi, Sara</creatorcontrib><creatorcontrib>Yasui, Hisateru</creatorcontrib><creatorcontrib>Shoji, Hirokazu</creatorcontrib><creatorcontrib>Shibata, Nobuhiro</creatorcontrib><creatorcontrib>Yamaguchi, Kensei</creatorcontrib><creatorcontrib>Esaki, Taito</creatorcontrib><creatorcontrib>Yabusaki, Hiroshi</creatorcontrib><creatorcontrib>Tsuji, Akihito</creatorcontrib><creatorcontrib>Kadowaki, Shigenori</creatorcontrib><creatorcontrib>Martinez Rodriguez, Jorge</creatorcontrib><creatorcontrib>Herrera Martinez, Marytere</creatorcontrib><creatorcontrib>Balancan, Paola</creatorcontrib><creatorcontrib>Castro Oliden, Victor</creatorcontrib><creatorcontrib>Grados, Julio</creatorcontrib><creatorcontrib>Hajac, Lukasz</creatorcontrib><creatorcontrib>Rha, Sun Young</creatorcontrib><creatorcontrib>Ryu, Min-Hee</creatorcontrib><creatorcontrib>Oh, Do-Youn</creatorcontrib><creatorcontrib>Orlova, Rashida</creatorcontrib><creatorcontrib>Tjulandin, Sergey</creatorcontrib><creatorcontrib>Chan, Sze</creatorcontrib><creatorcontrib>Landers, Gregory</creatorcontrib><creatorcontrib>Robertson, Barbara</creatorcontrib><creatorcontrib>Ruff, Paul</creatorcontrib><creatorcontrib>Rivera Herrero, Fernando</creatorcontrib><creatorcontrib>Miranda Poma, Jesus</creatorcontrib><creatorcontrib>Layos Romero, Laura</creatorcontrib><creatorcontrib>Dosso, Sara De</creatorcontrib><creatorcontrib>Yen, Chia-Jui</creatorcontrib><creatorcontrib>Chen, Yen-Yang</creatorcontrib><creatorcontrib>Oksuzoglu, Berna</creatorcontrib><creatorcontrib>Hacibekiroglu, Ilhan</creatorcontrib><creatorcontrib>Kolesnik, Oleksii</creatorcontrib><creatorcontrib>Kryzhanivska, Anna</creatorcontrib><creatorcontrib>Leshchenko, Lurii</creatorcontrib><creatorcontrib>Ilin, Ievgen</creatorcontrib><creatorcontrib>Voitko, Nataliia</creatorcontrib><creatorcontrib>Roy, Rajarshi</creatorcontrib><creatorcontrib>Shiu, Kai-Keen</creatorcontrib><creatorcontrib>Overton, Lindsay</creatorcontrib><creatorcontrib>Dunne, Richard</creatorcontrib><creatorcontrib>Dayyani, Farshid</creatorcontrib><creatorcontrib>Larson, Timothy</creatorcontrib><creatorcontrib>Kochenderfer, Mark</creatorcontrib><creatorcontrib>KEYNOTE-859 investigators</creatorcontrib><title>Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1–5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1–14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.
Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0–38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9–14·0] vs 11·5 months [10·6–12·1]; hazard ratio [HR] 0·78 [95% CI 0·70–0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6–14·2] vs 11·4 months [10·5–12·0]; 0·74 [0·65–0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8–19·3] vs 11·8 months [10·3–12·7]; 0·65 [0·53–0·79]; p<0·0001). The most common grade 3–5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified.
Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
Merck Sharp and Dohme.</description><subject>5-Fluorouracil</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adverse events</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>B7-H1 Antigen</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>ErbB-2 protein</subject><subject>Esophageal Neoplasms</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Intravenous administration</subject><subject>Leukocytes (neutrophilic)</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Monoclonal antibodies</subject><subject>Oxaliplatin</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Pembrolizumab</subject><subject>Placebos</subject><subject>Safety</subject><subject>Stomach Neoplasms - pathology</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>1470-2045</issn><issn>1474-5488</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkc1u1TAQhSMEoqXwCCBLbG6lBvwTOwkbhKpbiqgogrJgZfln0uvKiYOdXKk8VR8R597CAiGxsmf0zZnROUXxnOBXBBPx-iupalxSXPEVZccYc8JL8aA4zO2q5FXTPNz998hB8SSlG4xJTTB_XBywuqk5qdhhcfcZeh2Ddz_nXmk0-jkhs4E-TBuIarxFW4gp90avDOjwD6ALEZ2vv9BygGs1uS0gZbdqMGDRtUpTdAaZpYxo9XH9_dPl1bpseHv8BinUz35yBoYpwgmKarChdwnsCbJh1h5K7d2Qq3GjEiCGspbyT4tHnfIJnt2_R8W3s_XV6Xl5cfn-w-m7i9Kwlk2lqGhbcdMoQ60CZYVuDMOM61ZTU_OuZg3UlAtlO1tjLrJ_FneU09boTmnCjorVXneM4ccMaZL5NgPeqwHCnCRtmsVNUbUZffkXehPmOOTrFqoSeU-9UHxPmRhSitDJMbpexVtJsFwilbtI5ZKXpEzuIpUiz724V591D_bP1O8MM_B2D0C2Y-sgymQcLAG4CGaSNrj_rPgFATixqg</recordid><startdate>202311</startdate><enddate>202311</enddate><creator>Oh, 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Limited</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>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</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>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>202311</creationdate><title>Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial</title><author>Oh, Do-Youn ; Yañez, Patricio ; Bai, Yuxian ; Ryu, Min-Hee ; Rivera, Fernando ; Alves, Gustavo Vasconcelos ; Garrido, Marcelo ; Shiu, Kai-Keen ; Çil, Timuçin ; Pan, Hongming ; Wainberg, Zev A ; O'Connor, Juan Manuel ; Cundom, Juan ; Ng, Weng ; Peressoni, Mauricio ; Andrade, Carlos ; Alves, Gustavo ; Vianna, Karina ; Monteiro, Maria Marcela ; Tan, Ann ; Asselah, Jamil ; Mahave, Mauricio ; Salman, Pamela ; Liu, Tianshu ; Lin, Xiaoyan ; Li, Wei ; Qu, Yanli ; Chen, Ping ; Liang, Xinjun ; Zhao, Qun ; Yin, Xianli ; Li, Junhe ; Guerrero, Alvaro ; Rubiano, Juan ; Gonzalez Herrera, Ileana ; Melichar, Bohuslav ; Buchler, Tomas ; Svoboda, Tomas ; Vrana, David ; Cvek, Jakub ; Pfeiffer, Per ; Baeksgaard, Lene ; Yilmaz, Mette ; Boige, Valerie ; Lopez-Trabada, Daniel ; Hiret, Sandrine ; Arnold, Dirk ; Martens, Uwe ; Castro, Hugo ; Lopez, Karla ; Chivalan, Marco ; Chan, Wendy ; Horvath, Zsolt ; Lowery, Maeve ; Pelles Avraham, Sharon ; Di Bartolomeo, Maria ; Lonardi, Sara ; Yasui, Hisateru ; Shoji, Hirokazu ; Shibata, Nobuhiro ; Yamaguchi, Kensei ; Esaki, Taito ; Yabusaki, Hiroshi ; Tsuji, Akihito ; Kadowaki, Shigenori ; Martinez Rodriguez, Jorge ; Herrera Martinez, Marytere ; Balancan, Paola ; Castro Oliden, Victor ; Grados, Julio ; Hajac, Lukasz ; Rha, Sun Young ; Ryu, Min-Hee ; Oh, Do-Youn ; Orlova, Rashida ; Tjulandin, Sergey ; Chan, Sze ; Landers, Gregory ; Robertson, Barbara ; Ruff, Paul ; Rivera Herrero, Fernando ; Miranda Poma, Jesus ; Layos Romero, Laura ; Dosso, Sara De ; Yen, Chia-Jui ; Chen, Yen-Yang ; Oksuzoglu, Berna ; Hacibekiroglu, Ilhan ; Kolesnik, Oleksii ; Kryzhanivska, Anna ; Leshchenko, Lurii ; Ilin, Ievgen ; Voitko, Nataliia ; Roy, Rajarshi ; Shiu, Kai-Keen ; Overton, Lindsay ; Dunne, Richard ; Dayyani, Farshid ; Larson, Timothy ; Kochenderfer, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-642945c8ac2daead6b8c3035b9b2c75f738e7256adfd7056051d0f2529cbfab13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>5-Fluorouracil</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adverse events</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>B7-H1 Antigen</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>ErbB-2 protein</topic><topic>Esophageal Neoplasms</topic><topic>Esophagus</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Hepatitis</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Intravenous administration</topic><topic>Leukocytes (neutrophilic)</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Monoclonal antibodies</topic><topic>Oxaliplatin</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Pembrolizumab</topic><topic>Placebos</topic><topic>Safety</topic><topic>Stomach Neoplasms - pathology</topic><topic>Targeted cancer therapy</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oh, Do-Youn</creatorcontrib><creatorcontrib>Yañez, Patricio</creatorcontrib><creatorcontrib>Bai, Yuxian</creatorcontrib><creatorcontrib>Ryu, Min-Hee</creatorcontrib><creatorcontrib>Rivera, Fernando</creatorcontrib><creatorcontrib>Alves, Gustavo Vasconcelos</creatorcontrib><creatorcontrib>Garrido, Marcelo</creatorcontrib><creatorcontrib>Shiu, Kai-Keen</creatorcontrib><creatorcontrib>Çil, Timuçin</creatorcontrib><creatorcontrib>Pan, 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Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oh, Do-Youn</au><au>Yañez, Patricio</au><au>Bai, Yuxian</au><au>Ryu, Min-Hee</au><au>Rivera, Fernando</au><au>Alves, Gustavo Vasconcelos</au><au>Garrido, Marcelo</au><au>Shiu, Kai-Keen</au><au>Çil, Timuçin</au><au>Pan, Hongming</au><au>Wainberg, Zev A</au><au>O'Connor, Juan Manuel</au><au>Cundom, Juan</au><au>Ng, Weng</au><au>Peressoni, Mauricio</au><au>Andrade, Carlos</au><au>Alves, Gustavo</au><au>Vianna, Karina</au><au>Monteiro, Maria Marcela</au><au>Tan, Ann</au><au>Asselah, Jamil</au><au>Mahave, Mauricio</au><au>Salman, Pamela</au><au>Liu, Tianshu</au><au>Lin, Xiaoyan</au><au>Li, Wei</au><au>Qu, Yanli</au><au>Chen, Ping</au><au>Liang, Xinjun</au><au>Zhao, Qun</au><au>Yin, Xianli</au><au>Li, Junhe</au><au>Guerrero, Alvaro</au><au>Rubiano, Juan</au><au>Gonzalez Herrera, Ileana</au><au>Melichar, Bohuslav</au><au>Buchler, Tomas</au><au>Svoboda, Tomas</au><au>Vrana, David</au><au>Cvek, Jakub</au><au>Pfeiffer, Per</au><au>Baeksgaard, Lene</au><au>Yilmaz, Mette</au><au>Boige, Valerie</au><au>Lopez-Trabada, Daniel</au><au>Hiret, Sandrine</au><au>Arnold, Dirk</au><au>Martens, Uwe</au><au>Castro, Hugo</au><au>Lopez, Karla</au><au>Chivalan, Marco</au><au>Chan, Wendy</au><au>Horvath, Zsolt</au><au>Lowery, Maeve</au><au>Pelles Avraham, Sharon</au><au>Di Bartolomeo, Maria</au><au>Lonardi, Sara</au><au>Yasui, Hisateru</au><au>Shoji, Hirokazu</au><au>Shibata, Nobuhiro</au><au>Yamaguchi, Kensei</au><au>Esaki, Taito</au><au>Yabusaki, Hiroshi</au><au>Tsuji, Akihito</au><au>Kadowaki, Shigenori</au><au>Martinez Rodriguez, Jorge</au><au>Herrera Martinez, Marytere</au><au>Balancan, Paola</au><au>Castro Oliden, Victor</au><au>Grados, Julio</au><au>Hajac, Lukasz</au><au>Rha, Sun Young</au><au>Ryu, Min-Hee</au><au>Oh, Do-Youn</au><au>Orlova, Rashida</au><au>Tjulandin, Sergey</au><au>Chan, Sze</au><au>Landers, Gregory</au><au>Robertson, Barbara</au><au>Ruff, Paul</au><au>Rivera Herrero, Fernando</au><au>Miranda Poma, Jesus</au><au>Layos Romero, Laura</au><au>Dosso, Sara De</au><au>Yen, Chia-Jui</au><au>Chen, Yen-Yang</au><au>Oksuzoglu, Berna</au><au>Hacibekiroglu, Ilhan</au><au>Kolesnik, Oleksii</au><au>Kryzhanivska, Anna</au><au>Leshchenko, Lurii</au><au>Ilin, Ievgen</au><au>Voitko, Nataliia</au><au>Roy, Rajarshi</au><au>Shiu, Kai-Keen</au><au>Overton, Lindsay</au><au>Dunne, Richard</au><au>Dayyani, Farshid</au><au>Larson, Timothy</au><au>Kochenderfer, Mark</au><aucorp>KEYNOTE-859 investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2023-11</date><risdate>2023</risdate><volume>24</volume><issue>11</issue><spage>1181</spage><epage>1195</epage><pages>1181-1195</pages><issn>1470-2045</issn><issn>1474-5488</issn><eissn>1474-5488</eissn><abstract>PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1–5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1–14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.
Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0–38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9–14·0] vs 11·5 months [10·6–12·1]; hazard ratio [HR] 0·78 [95% CI 0·70–0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6–14·2] vs 11·4 months [10·5–12·0]; 0·74 [0·65–0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8–19·3] vs 11·8 months [10·3–12·7]; 0·65 [0·53–0·79]; p<0·0001). The most common grade 3–5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified.
Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.
Merck Sharp and Dohme.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>37875143</pmid><doi>10.1016/S1470-2045(23)00515-6</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2023-11, Vol.24 (11), p.1181-1195 |
| issn | 1470-2045 1474-5488 1474-5488 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2881710649 |
| source | MEDLINE; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | 5-Fluorouracil Adenocarcinoma Adenocarcinoma - drug therapy Adverse events Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - adverse effects B7-H1 Antigen Cancer therapies Chemotherapy Cisplatin Double-Blind Method Double-blind studies ErbB-2 protein Esophageal Neoplasms Esophagus Female Gastric cancer Hepatitis Humans Immunotherapy Intravenous administration Leukocytes (neutrophilic) Male Metastases Metastasis Monoclonal antibodies Oxaliplatin Patients PD-1 protein PD-L1 protein Pembrolizumab Placebos Safety Stomach Neoplasms - pathology Targeted cancer therapy Toxicity Tumors |
| title | Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T00%3A00%3A49IST&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=Pembrolizumab%20plus%20chemotherapy%20versus%20placebo%20plus%20chemotherapy%20for%20HER2-negative%20advanced%20gastric%20cancer%20(KEYNOTE-859):%20a%20multicentre,%20randomised,%20double-blind,%20phase%203%20trial&rft.jtitle=The%20lancet%20oncology&rft.au=Oh,%20Do-Youn&rft.aucorp=KEYNOTE-859%20investigators&rft.date=2023-11&rft.volume=24&rft.issue=11&rft.spage=1181&rft.epage=1195&rft.pages=1181-1195&rft.issn=1470-2045&rft.eissn=1474-5488&rft_id=info:doi/10.1016/S1470-2045(23)00515-6&rft_dat=%3Cproquest_cross%3E2881710649%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=2884672579&rft_id=info:pmid/37875143&rft_els_id=S1470204523005156&rfr_iscdi=true |