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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Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial.
Jeeyun Lee,Seung Tae Kim,Kyung Kim,Hyuk Lee,Iwanka Kozarewa,Peter G. Mortimer,Justin I. Odegaard,Elizabeth A. Harrington,Lee Ju Young,Taehyang Lee,Sung Yong Oh,Jung Hun Kang,Jung Hoon Kim,Youjin Kim,Jun Ho Ji,Young Saing Kim,Kyoung Eun Lee,Jinchul Kim,Tae Sung Sohn,Ji Yeong An,Min Gew Choi,Jun Ho Lee,Jae Moon Bae,Sung Kim,Jae J. Kim,Yang Won Min,Byung-Hoon Min,Nayoung K.D. Kim,Nayoung K.D. Kim,Sally Luke,Young Hwa Kim,Jung Yong Hong,Se Hoon Park,Joon Oh Park,Young Suk Park,Ho Yeong Lim,AmirAli Talasaz,Simon J. Hollingsworth,Kyoung-Mee Kim,Won Ki Kang +39 more
TL;DR: CtDNA analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib, and the biomarker-assigned treatment cohort had encouraging response rates and survival when compared to conventional 2L chemotherapy.
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Clinical impact of tumour biology in the management of gastroesophageal cancer
TL;DR: An overview of the key developments in the treatment of gastroesophageal cancer is provided, and potential strategies to further optimize therapy by targeting disease subtypes are discussed.
Journal ArticleDOI
Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity.
TL;DR: Various ‘next‐generation’ biomarker‐driven trial designs and their potentials and limitations to tackle recognized molecular heterogeneity challenges are discussed.
Journal ArticleDOI
Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.
Ismael Riquelme,Kathleen Saavedra,Jaime A. Espinoza,Helga Weber,Patricia García,Bruno Nervi,Marcelo Garrido,Alejandro H. Corvalan,Juan Carlos Roa,Carolina Bizama +9 more
TL;DR: An overview of the morphological classification, current treatment approaches, and molecular alterations that have been characterized for GC are provided and insights regarding emerging stem cell pathways are described, which may provide additional novel markers for the development of therapeutic agents against GC.
Journal ArticleDOI
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer.
Yung-Jue Bang,Jae Yong Cho,Yeul Hong Kim,Jin Won Kim,Maria Di Bartolomeo,Jaffer A. Ajani,Kensei Yamaguchi,Agnes Balogh,Teresa Sanchez,Markus Moehler +9 more
TL;DR: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC, however, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipILimumab in combination with other therapies for advanced gastric cancer.
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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