A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer

Kang, Yoon Koo; Rha, Sun Young; Tassone, Pierfrancesco; Barriuso, Jorge; Yu, Ronald; Szado, Tania; Garg, Amit; Bang, Yung Jue

doi:10.1038/bjc.2014.356

Cited by 81 publications

(56 citation statements)

References 45 publications

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“…In addition, no cases of cardiac failure or mortality due to cardiac toxicity were observed. Similarly, previous reports have shown that adding trastuzumab to chemotherapy does not increase the toxic effects associated with standard fluoropyrimidine and platinum chemotherapy (4,(16)(17)(18)(19). The toxicity profile of trastuzumab plus chemotherapy has been shown to be comparable to that for chemotherapy alone in phase II and III trials (4,20,21).…”

Section: No Patients -----------------------------------------------mentioning

confidence: 56%

“…High efficacy of trastuzumab has been confirmed prior to and following chemotherapy in patients with HER2-positive breast cancer, and expanded indications in gastric cancer are anticipated (14,15). Previous studies that have assessed chemotherapy plus trastuzumab treatment regimens for patients with HER2-positive gastric cancer have revealed good tolerance and high efficacy with cytotoxic chemotherapy including S-1 plus cisplatin, capecitabine plus oxaliplatin (or docetaxel), and cisplatin plus S-1, however, not capecitabine plus cisplatin (16)(17)(18)(19)(20)(21). Therefore, trastuzumab with cytotoxic chemotherapy is considered a standard treatment regimen for patients with HER2-positive gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

Namikawa

Munekage

et al. 2016

Molecular and Clinical Oncology

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Abstract. The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P= 0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. IntroductionGastric cancer is the third most commonly diagnosed cancer type worldwide and one of the leading causes of cancer-associated mortality (1). In patients with recurrent, metastatic, or advanced gastric cancer, chemotherapy can prolong survival and improve quality of life compared with the best supportive care.Human epidermal growth factor receptor (HER)2 is a member of a family of receptors that is associated with tumor cell proliferation, apoptosis, adhesion, migration and differentiation. It is overexpressed in 15-20% of patients with primary gastric and gastroesophageal junction cancers (2,3). Trastuzumab, a monoclonal antibody that targets HER2, induces antibody-dependent cellular cytotoxicity and inhibits HER2-mediated signaling by binding to the extracellular domain of HER2 (4). The trastuzumab for gastric cancer (ToGA) trial recently validated the additive effects of trastuzumab for HER2-positive, unresectable advanced or recurrent gastric cancer. This trial revealed a significant increase in the overall survival and progression-free survival when trastuzumab was used in combination with chemotherapy, thus supporting the use of trastuzumab in individualized, biomarker-based treatment (5). Additionally, it has been shown that second-line and later lines of chemotherapy can significantly improve patient outcomes, and that the additive...

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Section: No Patients -----------------------------------------------mentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

Namikawa

Munekage

et al. 2016

Molecular and Clinical Oncology

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“…Also, recurrent amplification of genes associated with the receptor tyrosine kinase pathway, such as EGFR, ERBB2, ERBB3, JAK2, FGFR2, and MET, and the angiogenesis pathway, such as VEGFA, have been reported in GC [4,5]. With the exception of a subset of patients with ERBB2 amplification who experienced benefits from trastuzumab [6], targeted agents for aberrant gene amplification have not yet been successful in therapeutic applications [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Signature of cytokines and angiogenic factors (CAFs) defines a clinically distinct subgroup of gastric cancer

et al. 2015

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Background Little is known about cytokine and angiogenic factors (CAFs) in gastric cancer (GC) in terms of tumor classification and prognostic value. Here, we aimed to correlate CAF signature with overall survival (OS) in GC. Methods We measured pretreatment serum levels of 52 kinds of CAFs in 68 GC patients who were treated with fluoropyrimidine and platinum combination chemotherapy using multiplex bead immunoassays and enzyme-linked immunosorbent assay. We evaluated correlations between CAF levels and pathological features and OS. Results Three distinct patient groups were identified: one with high levels of proangiogenic factors, another with high levels of proinflammatory factors, and the other with high levels of both factors. Eleven CAFs [interleukin (IL)-2 receptor-alpha, growth-regulated alpha protein, hepatocyte growth factor, macrophage colony-stimulating factor, stromal cell-derived factor, IL-6, IL-8, IL-10, interferongamma, vascular endothelial growth factor, and osteopontin] were independently correlated with poor OS. Clustering analysis of these 11 CAFs revealed distinct high and low 11-CAF signature groups. High 11-CAF signature was associated with shorter OS (10.1 vs. 17.9 months, p = 0.026) along with poor performance status, and the presence of signet ring cell components in multivariate analysis of OS (HR 1.76, p = 0.029). The patients' traditional clinicopathological characteristics were not significantly different between the high and low 11-CAF signature groups. Conclusion Serum CAF profiling differentiated GC patient groups. A high 11-CAF signature could identify GC patients with a poor prognosis when treated with standard chemotherapy who need urgent new treatment strategies.

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“…The administration of pertuzumab is approved for metastatic breast cancer [31] . The combination of pertuzumab and trastuzumab seems to be effective in advanced gastric cancer with overall response rates up to 86% [32] .…”

Section: Growth Factors Growth Factor Receptors and Downstream Featuresmentioning

confidence: 99%

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 phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer

Cited by 81 publications

References 45 publications

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

Signature of cytokines and angiogenic factors (CAFs) defines a clinically distinct subgroup of gastric cancer

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

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