scholarly journals Immune Checkpoint Inhibitors in Advanced Colorectal Cancer

2021 ◽  
Vol 9 (2) ◽  
pp. 71-74
Author(s):  
Jaekyung Cheon
Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2317 ◽  
Author(s):  
Federica Marmorino ◽  
Alessandra Boccaccino ◽  
Marco Maria Germani ◽  
Alfredo Falcone ◽  
Chiara Cremolini

The introduction of checkpoint inhibitors provided remarkable achievements in several solid tumors but only 5% of metastatic colorectal cancer (mCRC) patients, i.e., those with bearing microsatellite instable (MSI-high)/deficient DNA mismatch repair (dMMR) tumors, benefit from this approach. The favorable effect of immunotherapy in these patients has been postulated to be due to an increase in neoantigens due to their higher somatic mutational load, also associated with an abundant infiltration of immune cells in tumor microenvironment (TME). While in patients with dMMR tumors checkpoint inhibitors allow achieving durable response with dramatic survival improvement, current results in patients with microsatellite stable (MSS or MSI-low)/proficient DNA mismatch repair (pMMR) tumors are disappointing. These tumors show low mutational load and absence of “immune-competent” TME, and are intrinsically resistant to immune checkpoint inhibitors. Modifying the interplay among cancer cells, TME and host immune system is the aim of multiple lines of research in order to enhance the immunogenicity of pMMR mCRC, and exploit immunotherapy also in this field. Here, we focus on the rationale behind ongoing clinical trials aiming at extending the efficacy of immunotherapy beyond the MSI-high/dMMR subgroup with particular regard to academic no-profit studies.


2020 ◽  
Vol 9 (11) ◽  
pp. 3520
Author(s):  
Gerhard Jung ◽  
Daniel Benítez-Ribas ◽  
Ariadna Sánchez ◽  
Francesc Balaguer

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the immune contexture of the tumor microenvironment (TME) have enabled the development of new systemic treatments that boost the host immune system against the tumor—the immune checkpoint inhibitors (ICI). These promising drugs have already shown astonishing efficacies in other cancer types and have raised new hope for the treatment of metastatic CRC (mCRC). In this review, we will summarize the results of the clinical trials that led to their accelerated approval by the U.S. Food and Drug Administration (FDA) in 2017, as well as all relevant recent studies conducted since then—some of which are not published yet. We will focus on therapeutic efficacy, but also discuss the available data for drug safety and security, changes in quality of life indicators and predictive biomarkers for treatment response. The burgeoning evidence for a potential use of ICIs in other settings than mCRC will also be mentioned. For each trial, we have made a preliminary assessment of the quality of clinical trial design and of the “European Society of Medical Oncology (ESMO) magnitude of clinical benefit” (ESMO-MCBS) in order to provide the first evidence-based recommendation to the reader.


2020 ◽  
Vol 137 ◽  
pp. 117-126
Author(s):  
Patricia Martin-Romano ◽  
Samy Ammari ◽  
Yolla El-Dakdoukti ◽  
Capucine Baldini ◽  
Andreea Varga ◽  
...  

2021 ◽  
Vol 64 (5) ◽  
pp. 342-348
Author(s):  
Jin Won Kim

Immuno-oncological treatment approaches, particularly with the use of immune checkpoint inhibitors such as antiprogrammed death 1 (PD-1)/programmed death ligand 1 antibody or anti-cytotoxic T-lymphocyte associated protein 4 antibody, have become the standard treatment for gastrointestinal cancers. However, gastrointestinal cancers show an overall modest tumor response to immune checkpoint inhibitors. Nevertheless, subgroups such as tumors that are DNA mismatch repair-deficient or have high microsatellite instability particularly benefit from immune checkpoint inhibitors. Even in the first-line setting for colorectal cancer, the clinical efficacy of pembrolizumab, an anti–PD-1 antibody, was superior to that of chemotherapy. Recently, a combination of atezolizumab, an anti-programmed death ligand 1 antibody, and bevacizumab was approved as the first-line treatment for hepatocellular carcinoma, and was reported as superior to sorafenib. Nivolumab, an anti–PD-1 antibody that is added to chemotherapy as the first-line treatment for gastric cancer, resulted in longer survival compared with chemotherapy alone. Further studies are ongoing to investigate additional immune checkpoint inhibitors for other gastrointestinal cancers. This review aims to provide an overview of the results of clinical trials for immune checkpoint inhibitors in gastrointestinal cancers, including colorectal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer.


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