scholarly journals Clinical efficacy of immune checkpoint inhibitors in the treatment of unresectable advanced or recurrent gastric cancer: an evidence-based review of therapies

2018 ◽  
Vol Volume 11 ◽  
pp. 8239-8250 ◽  
Author(s):  
Kazuhiro Togasaki ◽  
Yasutaka Sukawa ◽  
Takanori Kanai ◽  
Hiromasa Takaishi
Keyword(s):  
Gastric Cancer ◽  
Clinical Efficacy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Evidence Based ◽  
Recurrent Gastric Cancer

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
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.

scholarly journals Current status of immune checkpoint inhibitors for gastric cancer

2020 ◽  
Vol 23 (4) ◽  
pp. 565-578 ◽  
Author(s):  
Koji Kono ◽  
Shotaro Nakajima ◽  
Kosaku Mimura
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Current Status

SLAMF8, a novel biomarker for personalized immune checkpoint blockade therapy in gastrointestinal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14078-e14078
Author(s):  
Qun Zhang ◽  
Lei Cheng ◽  
Jing Hu ◽  
Li Li ◽  
Mi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Normal Tissues ◽  
Ebv Infection

e14078 Background: Immune checkpoint inhibitors have brought great breakthroughs in cancer therapy. Activated immune response is known to be the prerequisite for exerting immunotherapy efficacy. Epstein-Barr virus (EBV) infection is associated with longer survival in gastric cancer (GC) patients due to enhanced anti-tumor immune response, and therefore it was reportedly played an important role in modulating immune checkpoint blockade therapy efficacy. However, molecular dimensions underlying the good response to immune checkpoint inhibitors in presence of EBV infection are still unclear. The aim of this study is to identify a gene signature related to EBV induced anti-tumor immune response, and select a tag gene from this signature to predict which patients are most likely to benefit from immune checkpoint blockade therapy. Methods: Two large transcriptome datasets from Gene Expression Omnibus(GEO) database (GSE51575 and GSE62254) were used to screen gene signature for EBV infected gastric cancer tissues. We further selected genes that showed a trend towards differential co-expression independent of EBV infection status. The tag gene of this differential co-expression signature was finally identified by bioinformatics analysis. To make an external validation, we performed RNA sequencing in 20 colorectal caner (CRC) tissues and 20 GC tissues, respectively. Meanwhile, tissue microarrays of CRC cohort (36 paired tumor and normal tissues) and GC cohort (75 paired tumor and normal tissues) were used to analyze the association of SLAMF8 with CD8 protein expression by immunohistochemistry (IHC). Results: Analysis of GEO datasets indicated 788 genes as feature gene cluster for EBV-positive gastric cancer, from which 290 genes were selected to be characterized by differential co-expression in either EBV-positive or EBV-negative gastric cancers. SLAMF8 was identified as the tag gene for this differential co-expression signature. This signature, tagged by SLAMF8, was successfully validated by our RNA sequencing data in presence of its good performance in dividing CRC and GC patients into two subsets. Moreover, we observed a significant association between SLAMF8 and CD8 expression in our CRC and GC tissue samples, in terms of either mRNA or protein level. Conclusions: SLAMF8, a potential indicator for T cell‐mediated immune response induced by EBV infection, may be served as a biomarker for individualized immune checkpoint blockade therapy in gastrointestinal cancer. Further SLAMF8 guided drug sensitivity tests are warranted to validate our results.

Clinical features, treatments and survival of HER2 positive gastric cancer with elevated alpha-fetoprotein: An analysis of 16 cases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16000-e16000
Author(s):  
Shaohua Ge ◽  
Yi Ba ◽  
Ting Deng ◽  
Yuchong Yang ◽  
Tao Ning ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Clinical Characteristics ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Elevated Serum ◽  
Her2 Positive ◽  
The Mean ◽  
Gastric Cancer Patients

e16000 Background: Gastric cancer with elevated alpha-fetoprotein (AFP) is a special type of gastric cancer with elevated serum AFP. It is often misdiagnosed as primary hepatic cancer due to abnormal AFP and liver metastasis. The AFP level is related to the prognosis of these patients in whom there is prone to high HER2 positive rate. Therefore, anti-HER2 treatment is optional, as well as the emerging immunotherapy with immune checkpoint inhibitors. Methods: Gastric cancer patients with HER2 and serum AFP examination were collected in our hospital from May 2017 till now. Serum AFP level over 7 ng/ml was defined as elevated AFP. The clinical characteristics, treatments and survival of the patients with HER2 positive and elevated AFP were picked and analyzed. Results: Among 135 gastric cancer patients with elevated AFP, 16 (11.9%) were HER-2 positive (12 with HER2 3+, 3 with HER2 2+/FISH+ and 1 with HER2 gene amplification in NGS). The mean serum AFP is 201.4± 476.7ng/ml (range: 7.74 -1335). There were 9 males and 7 females. The mean age was 55 years (range: 38-90). The tumors were located in stomach cardia and fundus in 5 cases, body in 5 cases, antrum in 4 cases, body and antrum in 1 case and whole stomach in 1 case. There were 2 patients in stage III and 14 patients in stage IV with metastasis to lymph node metastasis in 15, liver in 9, abdominal cavity in 3 and peritoneum in 3. As for the treatments, three patients underwent surgery, one of whom with exploratory laparotomy (no antitumor treatment after surgery, died from infection). In 13 advanced patients, 12 patients received systemic antitumor therapies (8 with chemotherapy+Trastuzumab+ immunotherapy, 2 with chemotherapy+Trastuzumab, 1 with chemotherapy+ immunotherapy and 1 with chemotherapy). The chemotherapy regimens were XELOX in 5 cases, SOX in 4 cases and FLOT in 2 cases. The response rate was 50% (6 in 12 patients) and the disease control rate was 100%. The median PFS was 7.5 months in first line therapy with six patients without progression disease yet. The longest PFS with PR lasted for 16.5 months with chemotherapy, trastuzumab and immune checkpoint inhibitor. Conclusions: Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics. Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors. This combination is expected to become a new regimen to improve survival of such special patients.

Sign in / Sign up

Export Citation Format

Share Document