scholarly journals PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 558 ◽  
Author(s):  
Alessandro Rizzo ◽  
Angela Dalia Ricci ◽  
Giovanni Brandi
Keyword(s):  
Biliary Tract ◽  
Anticancer Agents ◽  
Biliary Tract Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Tract Cancer ◽  
Predictors Of Response ◽  
Tumor Mutational Burden

Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers.

scholarly journals Current Progress and Future Perspectives of Immune Checkpoint Inhibitors in Biliary Tract Cancer

2021 ◽  
Vol Volume 14 ◽  
pp. 1873-1882
Author(s):  
Poshita-Kumari Seesaha ◽  
Kang-Xin Wang ◽  
Guo-Qun Wang ◽  
Ting-Yun Cui ◽  
Feng-Jiao Zhao ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Future Perspectives ◽  
Tract Cancer

scholarly journals Immunotherapy in Biliary Tract Cancer: Worthy of a Second Look

2020 ◽  
Vol 27 (3) ◽  
pp. 107327482094804 ◽  
Author(s):  
Angela Dalia Ricci ◽  
Alessandro Rizzo ◽  
Giovanni Brandi
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Published Data ◽  
Tract Cancer ◽  
Selection Of Patients ◽  
Selection Of

Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of several malignancies, the role of immunotherapy in biliary tract cancer (BTC) is currently under investigation and ICIs are still looking for their niche in this setting. In this Editorial, we discuss recently published data regarding ICIs in BTC, with a particular focus in terms of selection of patients and biomarker-driven trials.

scholarly journals Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1078 ◽  
Author(s):  
Amit Mahipal ◽  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Alexander Lim ◽  
Richard Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Hepatic Reserve ◽  
Dismal Prognosis ◽  
United States Food

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

scholarly journals Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3625
Author(s):  
Boris Duchemann ◽  
Jordi Remon ◽  
Marie Naigeon ◽  
Laura Mezquita ◽  
Roberto Ferrara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Circulating Biomarkers ◽  
Liquid Biopsies ◽  
Technical Requirements ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Immune checkpoint inhibitors are now a cornerstone of treatment for non-small cell lung cancer (NSCLC). Tissue-based assays, such as Programmed cell death protein 1 (PD-L1) expression or mismatch repair deficiency/microsatellite instability (MMRD/MSI) status, are approved as treatment drivers in various settings, and represent the main field of research in biomarkers for immunotherapy. Nonetheless, responses have been observed in patients with negative PD-L1 or low tumor mutational burden. Some aspects of biomarker use remain poorly understood and sub-optimal, in particular tumoral heterogeneity, time-evolving sampling, and the ability to detect patients who are unlikely to respond. Moreover, tumor biopsies offer little insight into the host’s immune status. Circulating biomarkers offer an alternative non-invasive solution to address these pitfalls. Here, we summarize current knowledge on circulating biomarkers while using liquid biopsies in patients with lung cancer who receive treatment with immune checkpoint inhibitors, in terms of their potential as being predictive of outcome as well as their role in monitoring ongoing treatment. We address host biomarkers, notably circulating immune cells and soluble systemic immune and inflammatory markers, and also review tumor markers, including blood-based tumor mutational burden, circulating tumor cells, and circulating tumor DNA. Technical requirements are discussed along with the current limitations that are associated with these promising biomarkers.

scholarly journals Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

2019 ◽  
Vol 38 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Yosuke Ando ◽  
Takahiro Hayashi ◽  
Reiko Sugimoto ◽  
Seira Nishibe ◽  
Kaori Ito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Heart Disease ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
History Of ◽  
Cancer Associated Thrombosis

SummaryPurpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.

PD-L1 expression as a prognostic marker in patients with advanced biliary tract cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16679-e16679
Author(s):  
Hyera Kim ◽  
Jung Yong Hong ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Group Analysis ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Tract Cancer ◽  
Positive Score ◽  
Combined Positive Score

e16679 Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered as a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score (CPS) positivity. Results: In all 186 patients, the median age was 62 years (range 38-82), and the primary tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 72 patients (38.7%), extrahepatic (EH)-CCC in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). There were 158 (84.9%) patients with recurrent disease and 28 (15.1%) with metastatic disease. Among the 186 patients, 53 (28.5%) had PD-L1 CPS positivity, and 133 were CPS negative. The median overall survival (OS) of patients with PD-L1 CPS positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. The OS and PFS were not statistically different between groups. In sub-group analysis, EH-CCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p= 0.002) and PFS (7.8 vs. 5.4 months, p= 0.005) than those that were PD-L1 negative. However, this finding was not reproduced in patients with IH-CCC or GB cancer. Univariate analysis of the association between PD-L1 expression and OS in patients with advanced BTC indicated that PD-L1 CPS positivity has a prognostic role in sub-populations older than 60 years (HR 1.743, CI 1.001-3.034, p = 0.050), those with EH-CCC (HR 2.449, CI 1.355-4.426, p = 0.003), and those with liver metastasis (HR 2.511, CI 1.362-4.626, p = 0.003). Conclusions: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EH-CCC but not for patients with IH-CCC or GB cancer.

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