scholarly journals The Efficacy of Immune Checkpoint Inhibitors as First-line Treatment in Microsatellite-instability-high Metastatic Colorectal Cancer

2021 ◽  
Vol 77 (5) ◽  
pp. 261-262
Author(s):  
Jong Yoon Lee
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

scholarly journals Gastrointestinal cancer treatment with immune checkpoint inhibitors

2021 ◽  
Vol 64 (5) ◽  
pp. 342-348
Author(s):  
Jin Won Kim
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Gastrointestinal Cancers ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
First Line Treatment

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.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

Relative risk of hematological toxicities in patients with advanced renal cell carcinoma treated with upfront immune checkpoint inhibitors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 675-675
Author(s):  
Nusrat Jahan ◽  
Somedeb Ball ◽  
Miguel Quirch ◽  
Shabnam Rehman ◽  
Kyaw Zin Thein ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Relative Risk ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
First Line Treatment

675 Background: Sunitinib was the standard first-line treatment of advanced renal cell carcinoma (aRCC) for the past decade, but it has been associated with significant hematological toxicities. Immune checkpoint inhibitors (ICI) based regimens have become the new preferred treatment for aRCC in the first-line setting. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hematological toxicities associated with upfront use of ICI-based regimens for aRCC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first-line treatment of aRCC were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Four phase 3 RCTs, CheckMate 214, IMmotion151, JAVELIN Renal 101 and KEYNOTE-426, randomizing 3706 patients were included in the analysis of anemia and thrombocytopenia. CheckMate 214 did not report the number of neutropenia. Hence, other 3 RCTs that included 2624 patients were analyzed for neutropenia. Following regimens were used in the study arms — CheckMate 214: nivolumab+ipilimumab, IMmotion151: atezolizumab+bevacizumab, JAVELIN Renal 101: axitinib+avelumab; and KEYNOTE-426: axitinib+ pembrolizumab. Sunitinib was used in the control arms for all the studies. The pooled RR of any-grade hematological toxicities are as follows — anemia: 0.31 (95% CI:0.24-0.41, P< 0.00001, I2=39%); thrombocytopenia: 0.11 (95% CI: 0.06-0.19, P<0.00001, I2=63%); neutropenia: 0.08 (95% CI: 0.05-0.13, P<0.00001, I2=0%). The pooled RR of grade 3 and higher hematological toxicities are as follows — anemia: 0.14 (95% CI:0.08-0.25, P< 0.00001, I2=0); thrombocytopenia: 0.06 (95% CI:0.02-0.16, P<0.00001, I2=4%); neutropenia: 0.06 (95% CI: 0.02-0.16, P<0.00001, I2=0%). Conclusions: ICI-based regimens have significantly reduced risk of any-grade as well as high-grade hematological toxicities compared to sunitinib in patients with aRCC.

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