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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Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: The GERCOR phase II trial ERaFOX.
Gérard Lledo,Florence Huguet,Benoist Chibaudel,Frédéric Di Fiore,Laurent Mineur,Marie-Pierre Galais,Pascal Artru,Valérie Blondin,Olivier Dupuis,Menouar Samir Abdiche,Nicolas Jovenin,Astrid Pozet,Franck Bonnetain,Mohamed Attia,Laetitia Dahan,Aimery de Gramont +15 more
TL;DR: Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated and unfortunately, these results were not confirmed in two recent phase III studies.
Journal ArticleDOI
Risk of anti-EGFR monoclonal antibody-related skin rash: an up-to-date meta-analysis of 25 randomized controlled trials
TL;DR: In patients with advanced solid tumors, EGFR-MoAbs are associated with an increased risk of developing skin rash and acne-like skin rash, and the risk tends to be associated with EGFR -monoclonal antibodies treatment duration.
Journal ArticleDOI
Predictive biomarkers for the efficacy of cetuximab combined with cisplatin and capecitabine in advanced gastric or esophagogastric junction adenocarcinoma: a prospective multicenter phase 2 trial
Xiaotian Zhang,Jianming Xu,Huilong Liu,Lin Yang,Jun Liang,Nong Xu,Yuxian Bai,Jiejun Wang,Lin Shen +8 more
TL;DR: S Severity of skin rash and TGF-α level correlated with efficacy, and EGFR overexpression might predict cetuximab efficacy are evaluated.
Journal ArticleDOI
Frequent Coamplification of Receptor Tyrosine Kinase and Downstream Signaling Genes in Japanese Primary Gastric Cancer and Conversion in Matched Lymph Node Metastasis.
Arnaldo N. S. Silva,Jordy Coffa,Varsha Menon,Lindsay C. Hewitt,Kakoli Das,Yohei Miyagi,Dan Bottomley,Hayley L. Slaney,Toru Aoyama,Wolfram Mueller,Tomio Arai,Iain Beehuat Tan,Niantao Deng,Xiu B. Chan,Patrick Tan,Akira Tsuburaya,Kentaro Sakamaki,Jeremy D. Hayden,Takaki Yoshikawa,Ilse Zondervan,Suvi Savola,Heike I. Grabsch,Heike I. Grabsch +22 more
TL;DR: This is the first and most comprehensive study in gastric cancer investigating the concordance between gene copy number status of targetable RTKs and downstream signaling oncogenes in primGC and LNmets.
Journal ArticleDOI
Influence of the HER receptor ligand system on sensitivity to cetuximab and trastuzumab in gastric cancer cell lines.
Julia Kneissl,Anja Hartmann,Nicole Pfarr,Franziska Erlmeier,Thomas Lorber,Simone Keller,Gwen Zwingenberger,Wilko Weichert,Birgit Luber +8 more
TL;DR: HB-EGF may be a useful marker for the prediction of trastuzumab sensitivity in gastric cancer and was effective in rescuing sensitive cell lines from inhibition of cell proliferation by both, cetuximab and trastudumab.
References
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TL;DR: The results for 20 world regions are presented, summarizing the global patterns for the eight most common cancers, and striking differences in the patterns of cancer from region to region are observed.
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New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
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Journal ArticleDOI
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Yung-Jue Bang,Eric Van Cutsem,A. Feyereislova,Hyun Cheol Chung,Lin Shen,Akira Sawaki,Florian Lordick,Atsushi Ohtsu,Yasushi Omuro,Taroh Satoh,G. Aprile,Evgeny Kulikov,Julie Hill,Michaela Lehle,Josef Rüschoff,Yoon-Koo Kang +15 more
TL;DR: Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.
Journal ArticleDOI
Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer
Jan B. Vermorken,Ricard Mesia,Fernando Rivera,Eva Remenar,Andrzej Kawecki,Sylvie Rottey,Jozsef Erfan,Dmytro Zabolotnyy,Heinz Roland Kienzer,Didier Cupissol,Frederic Peyrade,Marco Benasso,Ihor Vynnychenko,Dominique De Raucourt,Carsten Bokemeyer,Armin Schueler,Nadia Amellal,Ricardo Hitt +17 more
TL;DR: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracils) significantly prolonged the median overall survival and improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
Journal ArticleDOI
Capecitabine and oxaliplatin for advanced esophagogastric cancer.
TL;DR: Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer, in a two-by-two design.
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