A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma

Chan, Jennifer A.; Blaszkowsky, Lawrence S.; Enzinger, Peter C.; Ryan, David P.; Abrams, Thomas A.; Zhu, Andrew X.; Temel, Jennifer S.; Schrag, Deborah; Bhargava, Pankaj; Meyerhardt, J. A.; Wolpin, Brian M.; Fidias, P.; Zheng, Hui; Florio, Salvatore; Regan, Eileen; Fuchs, Charles S.

doi:10.1093/annonc/mdq604

Cited by 95 publications

(58 citation statements)

References 28 publications

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“…In particular, biological agents that target the epidermal growth factor and vascular endothelial growth factor when used in combination with conventional chemotherapy have shown encouraging efficacy data that may potentially improved survival in gastroesophageal cancer. 7,8 The ToGA study, a Phase III trial of trastuzumab added to standard chemotherapy in HER2 positive advanced gastric cancer demonstrated a median survival of 13.8 months in the trastuzumab plus chemotherapy arm compared to 11.1 months in the chemotherapy alone arm (p ¼ 0.0046) with significant improvement in time to progression (7.1 vs. 5.6 months, p ¼ 0.0003) and progression-free survival (6.7 vs. 5.5 months, p ¼ 0.0002) favoring the trastuzumab treated group with comparable toxicity profiles. 9 This established trastuzumab plus chemotherapy as standard of care in HER2-positive advanced gastric cancer.…”

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confidence: 99%

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Chua

Merrett

2011

Intl Journal of Cancer

164

111

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With the availability of a therapeutic target and an effective agent in trastuzumab, a systematic examination of the literature to investigate the role of human epidermal growth factor 2 (HER2) as a prognostic factor for survival and its association with clinicopathologic markers may improve treatment. An electronic search of the MEDLINE and PubMed databases (January 1990 to January 2011) was undertaken to identify translational studies that correlated HER2 with clinicopathologic markers and/or survival outcome. This review included 49 studies totaling 11,337 patients. Forty-four percent of patients had Stage I/II, and 56% had Stage III/IV disease. Immunohistochemistry was most commonly used to assess HER2 expression, identifying a median rate of 18% (range, 4-53%) of gastric cancer demonstrating HER2 overexpression. In patients with and without HER2 overexpression, the median 3-year disease-free survival rate was 58% (range, 50-88%) and 86% (range, 62-97%), respectively. Of the 35 studies reporting the impact of HER2 overexpression on survival, 20 studies (57%) reported no difference in overall survival, two studies (6%) reported significantly longer overall survival in patients with HER2 overexpression and 13 studies (37%) reported significantly poorer overall survival in patients with HER2 overexpression. The median overall survival and 5-year survival rate was 21 (range, 10-57) months and 42%, and 33 (range, 13-80) months and 52% in patients with and without HER2 overexpression, respectively. HER2 overexpression appears to be associated with poorer survival and with intestinal-type gastric cancer in this group of patients for whom majority undergone curative gastrectomy.On a global scale, gastric cancer remains the second most common cause of cancer-related death with an estimated 930,000 new cases diagnosed each year albeit an overall decline in incidence. 1 Noncardia gastric cancers have steadily declined. However, it has been observed that proximal gastric cancers (cardia and oesophago-gastric tumors) are increasing at a rate of up to 10% per year, far exceeding that of any other type of cancer. Metastatic or advanced unresectable gastric cancer is an aggressive malignancy with a poor prognosis despite chemotherapy treatment with median survival of 7.5 to 12 months and a median survival of 3 to 5 months if managed by best supportive care. 2 Gastric cancer is a chemosensitive disease where a range of chemotherapy agents may achieve response rates of 30 to 40%; however, in the advanced setting, the disease is limited by a low complete response rate and the response duration is protracted often leading to disease progression and treatment related toxicities. 3 Combination chemotherapy with a Japanese standard doublet of fluoropyrimidine and platinum or western triplet regimens has shown better response rates and outcomes over single agent chemotherapy. However, there remains no established global standard for treatment.The human epidermal growth factor 2 (HER2) gene is a proto-oncogene where high amplifica...

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confidence: 99%

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Chua

Merrett

2011

Intl Journal of Cancer

164

111

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“…A SWOG study in gastroesophageal junction and gastric adenocarcinomas resulted in responses in 9% of patients (11). Cetuximab in a similar population produced a response in 3% of patients (13). However, the only randomized phase III study of a single agent EGFR inhibitor, gefitinib in the second line setting in esophageal cancers (75% adenocarcinoma) in this case, did not demonstrate a survival benefit compared to placebo (3.73 months compared to 3.67 months) (14).…”

Section: Epidermal Growth Factor Receptor (Egfr)mentioning

confidence: 81%

Beyond HER2: recent advances and future directions in targeted therapies in esophagogastric cancers

Hwang¹

2016

J. Gastrointest. Oncol.

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Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas. Other promising approaches are being investigated, including targeted therapies such as MET and FGFR inhibitors, as well as immunotherapy and agents that may affect synthetic lethality.

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“…Individualized treatment of gastric cancer therapy revealed only a marginal benefit on the overall survival (7.1 mo) [17] . Moreover, cetuximab as a single agent administration for second line therapy resulted in even lower impact on the overall survival (3.6 to 4 mo) with poor response (9%) [18] . Cetuximab in combination with several cytostatic substances for neoadjuvant chemotherapy showed response rates up to 70% [19,20] .…”

Section: Growth Factors Growth Factor Receptors and Downstream Featuresmentioning

confidence: 97%

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

Dittmar

Settmacher

2015

WJGO

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Gastric cancer is one of the most common malignancies worldwide. The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved. A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome. With this intention, first steps have been made in the research of growth factor signaling. Regarding morphogens, cell cycle and nuclear factor-κB signaling, a remarkable count of target-specific agents have been developed, nevertheless the transfer into the field of clinical routine is still at the beginning. The potential utility of epigenetic targets and the further evaluation of microRNA signaling seem to have potential for the development of novel treatment strategies in the future.

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A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma

Cited by 95 publications

References 28 publications

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Beyond HER2: recent advances and future directions in targeted therapies in esophagogastric cancers

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

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