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
A graphical method to assess treatment-covariate interactions using the Cox model on subsets of the data
Marco Bonetti,Richard D. Gelber +1 more
TL;DR: The subpopulation treatment effect pattern plot (STEPP) method is introduced, designed to facilitate the interpretation of estimates of treatment effect derived from different but potentially overlapping subsets of clinical trial data.
Journal ArticleDOI
Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Florian Lordick,Birgit Luber,Sylvie Lorenzen,Susanna Hegewisch-Becker,Gunnar Folprecht,E. Woll,Thomas Decker,Esther Endlicher,N Rothling,Tibor Schuster,Gisela Keller,Falko Fend,Falko Fend,Christian Peschel +13 more
TL;DR: Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer and is at present being investigated in a phase III randomised controlled trial.
Journal ArticleDOI
Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.
Sae-Won Han,Sae-Won Han,Do-Youn Oh,Do-Youn Oh,Seock-Ah Im,Seock-Ah Im,Sook Ryun Park,Keun-Wook Lee,Hong-Suk Song,Nam-Su Lee,K. H. Lee,In Sil Choi,MH Lee,Min Ah Kim,Woo Ho Kim,Yung-Jue Bang,Yung-Jue Bang,Tae-You Kim,Tae-You Kim +18 more
TL;DR: Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment and potential predictive biomarkers potentially associated with efficacy were analysed.
Journal ArticleDOI
Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study)
Carmine Pinto,F. Di Fabio,Carlo Barone,Salvatore Siena,Alfredo Falcone,Stefano Cascinu,F. L. Rojas Llimpe,Giulia Maria Stella,Giovanni Schinzari,Salvatore Artale,V. Mutri,S. Giaquinta,Laura Giannetta,Alberto Bardelli,Andrea Martoni +14 more
TL;DR: The addition of cetuximab to the cisplatin/ docetaxel regimen improved the ORR of the cisPlatin/docetaxe doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS.
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