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

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.

Download Full-text

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

Cancers ◽

10.3390/cancers13030558 ◽

2021 ◽

Vol 13 (3) ◽

pp. 558 ◽

Cited By ~ 4

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.

Download Full-text

PSY7-4 Current status and future perspectives in biliary tract cancer in Singapore

Annals of Oncology ◽

10.1016/j.annonc.2021.05.410 ◽

2021 ◽

Vol 32 ◽

pp. S244

Author(s):

Su Pin Choo

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Current Status ◽

Future Perspectives ◽

Tract Cancer

Download Full-text

Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms22137201 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7201

Author(s):

In-Ho Kim ◽

Hyo-Jin Lee

Keyword(s):

Bladder Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Systemic Treatment ◽

Checkpoint Inhibitors ◽

Invasive Bladder Cancer ◽

Current Evidence ◽

Future Perspectives ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16679 ◽

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.

Download Full-text

Durable response of immune checkpoint inhibitor after failure of gemcitabine-based chemotherapy for a patient with metastatic biliary tract cancer

Journal of Cancer Research and Practice ◽

10.4103/jcrp.jcrp_22_21 ◽

2021 ◽

Vol 8 (4) ◽

pp. 152

Author(s):

Chiun Hsu ◽

Chien-Huai Chuang

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Durable Response ◽

Tract Cancer

Download Full-text

Immune checkpoint inhibitors for treatment of advanced gastric or gastroesophageal junction cancer: Current evidence and future perspectives

Chinese Journal of Cancer Research ◽

10.21147/j.issn.1000-9604.2020.03.02 ◽

2020 ◽

Vol 32 (3) ◽

pp. 287-302

Author(s):

Zhening Zhang ◽

◽

Tong Xie ◽

Xiaotian Zhang ◽

Changsong Qi ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Gastroesophageal Junction ◽

Current Evidence ◽

Future Perspectives ◽

Gastroesophageal Junction Cancer

Download Full-text

Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003214 ◽

2021 ◽

Vol 9 (11) ◽

pp. e003214

Author(s):

Xiaofeng Chen ◽

Deqiang Wang ◽

Jing Liu ◽

Jingrong Qiu ◽

Jun Zhou ◽

...

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Poor Prognosis ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Chinese Patients ◽

Genomic Alterations ◽

Early Stage Disease ◽

Tract Cancer

BackgroundRecently, immunotherapy with immune checkpoint inhibitors (ICIs) has shown promising efficacy in biliary tract cancer (BTC), which includes gallbladder cancer (GBC) and cholangiocarcinoma (CHOL). Understanding the association between immunotherapy outcomes and the genomic profile of advanced BTC may further improve the clinical benefits from immunotherapy.MethodsGenomic tumor DNA was isolated from 98 Chinese patients with advanced BTC and used for targeted next-generation sequencing of 416 cancer-related genes to identify the genomic alterations common to advanced BTC. Thirty-four patients had received ICI camrelizumab plus gemcitabine and oxaliplatin (from the NCT03486678 trial) as a first-line treatment. Tumor-infiltrating immune cells were evaluated using immunofluorescence staining.ResultsKRAS and TP53 mutations were much more frequent in the advanced-stage BTC cohort than in other cohorts with mostly early stage disease. Specifically, KRAS-TP53 co-mutations were favored in advanced CHOL, with a favorable response to immunotherapy, while single KRAS mutations predicted poor prognosis and immunotherapy outcomes for CHOL. Compared with GBC, CHOL had more mutations in genes involved in KRAS signaling; a high mutation load in these genes correlated with poor immunotherapy outcomes and may subsequently cause inferior immunotherapy outcomes for CHOL relative to GBC. Furthermore, a genomic signature including 11 genes was developed; their mutated subtype was associated with poor prognosis and immunotherapy outcomes in both CHOL and GBC. Transcriptome analyses suggested immune dysfunction in the signature mutated subtype, which was validated by tumor microenvironment (TME) evaluation based on detection of immune cell infiltration. Importantly, the signature wild-type subtype with favorable TME may be an advantageous population of immunotherapy.ConclusionsGenomic alterations in advanced BTC were associated with specific prognosis and immunotherapy outcomes. Combining genomic classification with TME evaluation further improved the stratification of immunotherapy outcomes.

Download Full-text