Multimodality Treatment in Metastatic Gastric Cancer: From Past to Next Future

Gastric cancer (GC) still remains an incurable disease in almost two-thirds of the cases. However, a deeper knowledge of its biology in the last few years has revealed potential biomarkers suitable for tailored treatment with targeted agents. This aspect, together with the improvement in early supportive care and a wiser use of the available cytotoxic drugs across multiple lines of treatment, has resulted in incremental and progressive survival benefits. Furthermore, slowly but surely, targeted therapies and immune checkpoint inhibitors are revising the therapeutic scenario even in metastatic GC and especially in particular subgroups. Moreover, important study results regarding the possible role of an integrated approach combining systemic, surgical, and locoregional treatment in carefully selected oligometastatic GC patients are awaited. This review summarizes the state-of-the-art and the major ongoing trials involving a multimodal treatment of metastatic GC.

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New drug developments in metastatic gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818808072 ◽

2018 ◽

Vol 11 ◽

pp. 175628481880807 ◽

Cited By ~ 6

Author(s):

Aaron C. Tan ◽

David L. Chan ◽

Wasek Faisal ◽

Nick Pavlakis

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Targeted Therapies ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Predictive Biomarkers ◽

Metastatic Gastric Cancer ◽

New Era

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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Efficacy of Immune Checkpoint Inhibitors in Metastatic Epstein-Barr Virus Associated Gastric Cancer (EBVaGC): A Case Series and Review of Literature

10.21203/rs.3.rs-967167/v1 ◽

2021 ◽

Author(s):

Shimeng Liang ◽

Weibing Leng ◽

Dan Jiang ◽

Ming Liu ◽

Dan Cao ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Immune Checkpoint Inhibitors ◽

Epstein Barr Virus ◽

Checkpoint Inhibitors ◽

Case Series ◽

Metastatic Gastric Cancer ◽

Pooled Analysis ◽

Barr Virus ◽

Epstein Barr

Abstract Background Immunotherapy has revolutionized the treatment of malignant tumors. However, limited clinical data are available to report the efficacy of immune checkpoint inhibitors (ICIs) on Epstein-Barr virus-associated gastric carcinoma. Methods In this study, we report a case series of five patients with metastatic Epstein-Barr virus-associated gastric carcinoma who were treated with ICIs and to perform a pooled analysis of published cases to investigate the efficacy of ICIs in Epstein-Barr virus-associated gastric carcinoma patients. Results Between 2018 and 2020, five metastatic gastric cancer patients with EBV positivity who received PD-1 antibodies treatment were included in the analysis at the authors’ institution. Furthermore, we performed a pooled analysis of the contemporary literature. In our case series, two patients experienced partial response (PR); one patient achieved complete response (CR), whereas two patients had progression disease (PD), resulting an ORR of 60%. In the pooled analysis of all 36 patients, ORR was 48.6% (17/35). For the first line and later lines, it was 75% (3/4) and 45.2% (14/31) respectively. The ORR was 46.7% (14/30) for ICIs monotherapy and improved to 60% (3/5) by combination with chemotherapy. Conclusions These results demonstrated that an EBV-positive status was a reliable biomarker for immunotherapy in metastatic gastric cancer, especially for monotherapy. Immunotherapy combined with chemotherapy may be a better strategy, warranting further large-scale clinical trials for validation.

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SME network relationships and competitive strategies in the agri-food sector

European Business Review ◽

10.1108/ebr-08-2019-0150 ◽

2020 ◽

Vol 32 (3) ◽

pp. 405-424 ◽

Cited By ~ 2

Author(s):

Luca Camanzi ◽

Carlo Giua

Keyword(s):

Conceptual Model ◽

Network Structure ◽

Competitive Strategy ◽

Integrated Approach ◽

Business Networks ◽

Business Network ◽

Content Type ◽

Stakeholder Relationships ◽

Study Results

Purpose The purpose of this paper is to identify the main factors influencing agri-food small and medium enterprises (SMEs) participation in business networks and to evaluate the impacts of these factors on network structure and the ensuing competitive strategy. Design/methodology/approach The study is articulated in four main steps. First, a critical literature review is conducted concerning the main approaches to firm competitive advantage and the role of stakeholder relationships. Then, three research questions are formulated and discussed in the light of two case studies describing the implementation of an innovative contractual solution in Italy (i.e. business network contracts). Finally, based on these findings, a set of more general “propositions” are stated and included in a provisional conceptual model that schematically depicts an integrated vision of the antecedents and mechanisms influencing SMEs business network structure and competitive strategy. Findings The study results pointed out the opportunity to adopt an integrated approach, combining resource-based view and stakeholder causal scope approaches. The provisional conceptual model proposed illustrates the role of both external and internal resources and relational constructs to shaping network structure and competitive strategy. Originality/value The study’s contribution is twofold. First, the empirical study shed light on opportunities and limits of two business networks with different backgrounds, approaches and outcomes towards value creation. Second, the conceptual framework proposed advances our understanding and knowledge of the factors and mechanisms influencing SMEs business network structure and competitive strategy.

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The Crosstalk between Microbiome and Immune Response in Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21186586 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6586

Author(s):

Rihab Nasr ◽

Ali Shamseddine ◽

Deborah Mukherji ◽

Farah Nassar ◽

Sally Temraz

Keyword(s):

Gastric Cancer ◽

Immune Response ◽

Gut Microbiome ◽

Tumor Antigens ◽

Checkpoint Inhibitors ◽

Specific Antigen ◽

Cell Responses ◽

Host Epithelium ◽

H Pylori

Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host’s immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk between the gut microbiome and immune response in gastric cancer.

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Multimodality Approaches to Localized Gastric Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2010.0031 ◽

2010 ◽

Vol 8 (4) ◽

pp. 417-425 ◽

Cited By ~ 3

Author(s):

Prajnan Das ◽

Yixing Jiang ◽

Jeffrey H. Lee ◽

Manoop S. Bhutani ◽

William A. Ross ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Laparoscopic Surgery ◽

Adjuvant Chemotherapy ◽

Treatment Options ◽

Multimodality Treatment ◽

Primary Treatment ◽

Preoperative Chemoradiation ◽

Perioperative Chemotherapy

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.

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Population-based analysis of multimodality treatment of gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.124 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 124-124

Author(s):

P. Cen ◽

Y. Xing ◽

C. J. Wray ◽

M. B. Fallon ◽

V. I. Machicao ◽

...

Keyword(s):

Gastric Cancer ◽

Locally Advanced ◽

Community Setting ◽

Multimodality Treatment ◽

Population Based ◽

Entire Group ◽

Perioperative Chemotherapy ◽

Trimodality Therapy

124 Background: Limited data is available for the role of multimodality management for gastric adenocarcinoma and its outcome in the community. Methods: We retrospectively reviewed the outcomes for 341 patients (pts) who were diagnosed with gastric cancer in a community-based health-care system, including 9 hospitals, from 2000 to 2009. Results: 148/341 pts had undergone surgery and were included in the analysis. Median age at diagnosis was 68 year (range: 32-96), 56% were male, 55% were Caucasian and 25% were black. The stage distribution was as follows: 27% (40 pts) localized, 61% (90 pts) locally advanced and 12% (18 pts) with distant metastasis. 98 pts (66%) received surgery alone, 22 pts (15%) received perioperative chemotherapy, and 28 pts (19%) received perioperative chemo-radiation. After a median follow-up time of 5.2 yrs, the median OS for the entire group was 1.9 years, and 88 deaths had occurred at the last follow up. By stage, the median OS was 7 yrs, 2.3 yrs, and 0.3 yrs for localized stage, regional stage, and metastatic disease, respectively. The 5-yr survival was significantly better in pts who received perioperative chemo-radiation (68%), compared to those who received with surgery alone (33%) or perioperative chemotherapy (0%) (p=0.002). The 5-yr survivals by stage and treatment are shown in the table. Conclusions: Perioperative chemo-radiation was associated with a significantly better OS compared to surgery alone. Trimodality therapy for gastric cancer appears to be underutilized in the community setting described here. The survival advantage of surgery plus chemoradiation compared to surgery plus chemotherapy remains controversial and should be investigated in clinical trials. [Table: see text] No significant financial relationships to disclose.

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The role of the gastrectomy on survival in metastatic gastric cancer patients: A multicenter study of Anatolian Society of Medical Oncology (ASMO).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e15052 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e15052-e15052

Author(s):

Ozan Yazici ◽

Nuriye Ozdemir ◽

Ayse Ocak Duran ◽

Serkan Menekse ◽

Mehmet Ali Nahit Sendur ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Multicenter Study ◽

Medical Oncology ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Patients

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The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms221910719 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10719

Author(s):

Nadia Bolandi ◽

Afshin Derakhshani ◽

Nima Hemmat ◽

Amir Baghbanzadeh ◽

Zahra Asadzadeh ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Poor Response ◽

Cell Responses ◽

B7 Family ◽

Heterogeneous Nature ◽

Gastric Cancer Treatment ◽

Regulatory Ligands

Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC.

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The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819869767 ◽

2019 ◽

Vol 12 ◽

pp. 175628481986976 ◽

Cited By ~ 6

Author(s):

Gagandeep Brar ◽

Manish A. Shah

Keyword(s):

Gastric Cancer ◽

Immune Checkpoint Inhibitors ◽

Standard Treatment ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Gastroesophageal Junction ◽

Response To Treatment ◽

Gastroesophageal Junction Adenocarcinoma ◽

Tumor Types

Gastric cancer is a leading cause of cancer-related death worldwide. Recent evidence suggests that gastric cancer is a complex and heterogenous disease with emerging subtypes shown to affect response to treatment and survival. Immunotherapy is an advancing field and immune checkpoint inhibitors have become standard treatment options in numerous tumor types. In this review, we discuss the current and evolving use of checkpoint blockade, focusing on the anti-PD-1 inhibitor, pembrolizumab, for use in advanced gastric and gastroesophageal cancers.

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