Journal ArticleDOI
Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial
Florian Lordick,Yoon-Koo Kang,Hyun Cheol Chung,Pamela Salman,Sang Cheul Oh,György Bodoky,G. Kurteva,Constantin Volovat,Vladimir Moiseyenko,Vera Gorbunova,Joon Oh Park,Akira Sawaki,Ilhan Celik,Heiko Götte,Helena Melezínková,Markus Moehler +15 more
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TLDR
Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in the EXPAND trial.Abstract:
Summary Background Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m 2 (on days 1–14) and intravenous cisplatin 80 mg/m 2 (on day 1), with or without weekly cetuximab (400 mg/m 2 initial infusion on day 1 followed by 250 mg/m 2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2–5·5) compared with 5·6 months (5·1–5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92–1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3–4 adverse events, including grade 3–4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3–4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3–4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding Merck KGaA.read more
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Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial
Hansjochen Wilke,Kei Muro,Eric Van Cutsem,Sang Cheul Oh,György Bodoky,Yasuhiro Shimada,Shuichi Hironaka,Naotoshi Sugimoto,Oleg Lipatov,Tae You Kim,David Cunningham,Philippe Rougier,Yoshito Komatsu,Jaffer A. Ajani,Michael Emig,Roberto Carlesi,David Ferry,Kumari Chandrawansa,Jonathan D. Schwartz,Atsushi Ohtsu +19 more
TL;DR: The combination of ramucirumab with pac litaxel significantly increases overall survival compared with placebo plus paclitaxel, and could be regarded as a new standard second-line treatment for patients with advanced gastric cancer.
Journal ArticleDOI
Chemotherapy for advanced gastric cancer
Anna Dorothea Wagner,Nicholas Syn,Markus Moehler,Wilfried Grothe,Wei Peng Yong,Bee Choo Tai,Jingshan Ho,Susanne Unverzagt +7 more
TL;DR: Assessment of the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC.
Journal ArticleDOI
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.
Yelena Y. Janjigian,Yelena Y. Janjigian,Kohei Shitara,Markus Moehler,Marcelo Garrido,Pamela Salman,Lin Shen,Lucjan Wyrwicz,Kensei Yamaguchi,Tomasz Skoczylas,Arinilda Silva Campos Bragagnoli,Tianshu Liu,Michael Schenker,Patricio Eduardo Yanez,Mustapha Tehfe,Ruben Dario Kowalyszyn,Michalis V. Karamouzis,Ricardo Bruges,Thomas Zander,Roberto Pazo-Cid,Erika Hitre,Kynan Feeney,James M. Cleary,Valerie Poulart,Dana Cullen,Ming Lei,H. Xiao,Kaoru Kondo,M. Li,Jaffer A. Ajani +29 more
TL;DR: The CheckMate 649 trial as discussed by the authors evaluated first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophage alogaryal adenocarcinoma.
Journal ArticleDOI
Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial
T. Waddell,Ian Chau,David Cunningham,David Gonzalez,Alicia Frances Clare Okines,Andrew Wotherspoon,C. Saffery,Gary Middleton,Jonathan Wadsley,David R. Ferry,Wasat Mansoor,Tom Crosby,Fareeda Y. Coxon,David J. Smith,Justin S. Waters,Timothy Iveson,Stephen Falk,Sarah Slater,Clare Peckitt,Yolanda Barbachano +19 more
TL;DR: Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma.
Journal ArticleDOI
Current treatment and recent progress in gastric cancer.
TL;DR: Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide as mentioned in this paper, therefore, multidisciplinary treatment is paramount to treatment selection.
References
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Journal ArticleDOI
Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial.
Robert Pirker,José Rodrigues Pereira,Aleksandra Szczesna,Joachim von Pawel,Maciej Krzakowski,Rodryg Ramlau,Ihor Vynnychenko,Keunchil Park,Chih Teng Yu,Valentyn Ganul,Jae Kyung Roh,Emilio Bajetta,Kenneth J. O'Byrne,Filippo de Marinis,Wilfried Eberhardt,Thomas Goddemeier,M. Emig,Ulrich Gatzemeier +17 more
TL;DR: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer.
Journal ArticleDOI
Assessment of a HER2 scoring system for gastric cancer: results from a validation study.
Manfred Hofmann,O. Stoss,Daren Shi,R Büttner,M.J. van de Vijver,Won Ho Kim,A Ochiai,Josef Rüschoff,Thomas Henkel +8 more
TL;DR: The aim was to establish a HER2 scoring system for gastric cancer to identify suitable patients for enrolment in a trial of trastuzumab (Herceptin®) in advanced metastatic Gastric cancer.
Journal ArticleDOI
HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target
C. Gravalos,Antonio Jimeno +1 more
TL;DR: This review summarizes the rationale, preclinical evidence, retrospective clinical analyses, and the interim clinical data pertaining HER2 therapies in gastric cancer.
Journal ArticleDOI
Chemotherapy for advanced gastric cancer
Anna Dorothea Wagner,Nicholas Syn,Markus Moehler,Wilfried Grothe,Wei Peng Yong,Bee Choo Tai,Jingshan Ho,Susanne Unverzagt +7 more
TL;DR: Assessment of the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC.
Journal ArticleDOI
Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial
Timothyn Stanley Maughan,Richard Adams,Christopher Smith,A Meade,Matthew T. Seymour,Richard H. Wilson,Shelley Idziaszczyk,Rebecca Harris,David Fisher,S Kenny,Edward Kay,Jenna K. Mitchell,A Madi,Bharat Jasani,Michelle D. James,John Bridgewater,M. John Kennedy,Bart Claes,Diether Lambrechts,Richard Kaplan,Jeremy Peter Cheadle +20 more
TL;DR: This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours.
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