Candidate biomarker analyses in gastric or gastro-esophageal junction carcinoma: REGARD trial of single-agent ramucirumab (RAM) vs. placebo (PL).

Fuchs, Charles S.; Tabernero, Josep; Tomášek, Jiří; Chau, Ian; Melichar, Bohuslav; Safran, Howard; Tehfé, Mustapha; Dumitru, Filip; Topuzov, Eldar; Schlittler, Luís Alberto; Udrea, Anghel Adrian; Campbell, William; Brincat, Stephen; Emig, Michael; Melemed, Symantha; Hozak, Rebecca R.; Ferry, David; Caldwell, William; Ajani, Jaffer A.

doi:10.1200/jco.2015.33.15_suppl.4029

Cited by 6 publications

(5 citation statements)

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“…An assessment on the role of angiopoietin-2 as a prognostic biomarker based on the AVAGAST study data demonstrated that baseline angiopoietin-2 levels correlate with liver metastasis across ethnic groups and that angiopoietin- 2 may be a predictive biomarker for gastric cancer [ 63 ]. In the phase III REGARD study, analysis of biomarkers showed that HER2; VEGFR-1, -2, -3; and VEGF-C, -D were not markers for ramucirumab efficacy [ 64 ]. In multiple phase II studies of sunitinib, tumor VEGF-C expression was associated with significantly shorter median PFS (1.23 months vs. 2.86 months, log-rank p=0.0119) [ 43 ], and high sKIT (p=0.0081) and low VEGF-C (p=0.0326) were significantly associated with clinical benefit [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Chen

Ryu

et al. 2017

Cancer Res Treat

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Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

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Section: Resultsmentioning

confidence: 99%

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Chen

Ryu

et al. 2017

Cancer Res Treat

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“…It is shown that VEGF and their receptors are overexpressed in GC [98] . In this regard, Ramucirumab, a fully human IgG1 antibody against VEGFR2, is now approved by FDA for the treatment GC [99] .…”

Section: Treatment Of Gastric Cancermentioning

confidence: 99%

Molecular Signaling in Tumorigenesis of Gastric Cancer

Molaei

Forghanifard

Fahim

et al. 2018

IBJ

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Gastric cancer (GC) is regarded as the fifth most common cancer and the third cause of cancer-related deaths worldwide. Mechanism of GC pathogenesis is still unclear and relies on multiple factors, including environmental and genetic characteristics. One of the most important environmental factors of GC occurrence is infection with Helicobacter pylori that is classified as class one carcinogens. Dysregulation of several genes and pathways play an essential role during gastric carcinogenesis. Dysregulation of developmental pathways such as Wnt/β-catenin signaling, Hedgehog signaling, Hippo pathway, Notch signaling, nuclear factor-kB, and epidermal growth factor receptor have been found in GC. Epithelial-mesenchymal transition, as an important process during embryogenesis and tumorigenesis, is supposed to play a role in initiation, invasion, metastasis, and progression of GC. Although surgery is the main therapeutic modality of the disease, the understanding of biological processes of cell signaling pathways may help to develop new therapeutic targets for GC.

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“… 55 Other studies of tumour VEGF-C, VEGFR-3 and PDGFRa and plasma VEGF-C/D and VEGFR-1/3 have failed to yield a predictive biomarker of response. 51 , 56 , 57 An area of evolving research is the role of VEGF-related single nucleotide polymorphisms (SNPs). Candidate SNPs predicting favourable response to bevacizumab, 58 identified via a Monte Carlo study of 300 gastric cancer patients, were differentially distributed among White, Hispanic and Japanese patients, perhaps in part explaining the differential outcomes by geographical region observed in the INTEGRATE and AVAGAST trials.…”

Section: Anti-angiogenesismentioning

confidence: 99%

“…55 Other studies of tumour VEGF-C, VEGFR-3 and PDGFRa and plasma VEGF-C/D and VEGFR-1/3 have failed to yield a predictive biomarker of response. 51,56,57…”

Section: Anti-angiogenesismentioning

confidence: 99%

New drug developments in metastatic gastric cancer

Tan

Chan

Faisal

et al. 2018

Therap Adv Gastroenterol

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Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

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Candidate biomarker analyses in gastric or gastro-esophageal junction carcinoma: REGARD trial of single-agent ramucirumab (RAM) vs. placebo (PL).

Cited by 6 publications

References 0 publications

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Molecular Signaling in Tumorigenesis of Gastric Cancer

New drug developments in metastatic gastric cancer

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