New and emerging treatment options for biliary tract cancer

New Treatment Options for Advanced Biliary Tract Cancer

Current Treatment Options in Oncology ◽

10.1007/s11864-020-00767-3 ◽

2020 ◽

Vol 21 (8) ◽

Cited By ~ 4

Author(s):

Jonathan D. Mizrahi ◽

Rachna T. Shroff

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Treatment Options ◽

Tract Cancer ◽

New Treatment

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Epigenomic analysis of biliary tract cancer identifies subtypes with different immune characteristics and clinical outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16153 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16153-e16153

Author(s):

Zhiquan Qiu ◽

Jun Ji ◽

Yu Xu ◽

Yan Zhu ◽

Chun-Fang Gao ◽

...

Keyword(s):

Dna Methylation ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Immune Cell ◽

Treatment Options ◽

Molecular Heterogeneity ◽

Consensus Clustering ◽

Methylation Change ◽

Lasso Regression ◽

Tract Cancer

e16153 Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited treatment options. The epigenome-associated multi-dimensional studies for BTC are limited. Here, we proposed a DNA methylation-based classification scheme and investigated the associations between methylation and multi-dimensional data including clinicopathological features, genetic aberrations, and prognosis. Methods: Multi-dimensional data concerning mutation, DNA methylation, and clinical data from 105 BTC patients who received surgical resection (gallbladder cancer [GBC], n=48, cholangiocarcinoma [CCA], n=57) were analyzed. Differentially methylated blocks (DMBs) in GBCs and CCAs were identified by comparing tumors and adjacent tissues. Methylation-based subtyping was performed via non-supervised consensus clustering. Results: The differentially methylated blocks (DMBs) in GBCs and CCAs are highly overlapping. Based on the common DMBs of GBCs and CCAs, the classifier yielded high sensitivity of 95.2% and specificity of 96.0%. Hypomethylated genes were enriched in pathways of transmemberane receptor and ion binding, while hypermethylation occurred in genes concerning DNA binding transcription activity. By non-supervised clustering of common DMBs, 6 clusters with different degrees of methylation change were identified. Higher methylation alteration (cluster risk-high) was associated with more copy number variation and shorter OS. By LASSO regression, a 12-gene prognostic model was trained and validated (Table). As for immune characteristics, the methylation of CD8A gene was lower in the cluster risk-high group, and this association was validated in the TCGA-cholangiocarcinoma cohort. In addition, lower methylation change was associated with higher BCR/TCR diversity, immune cell infiltration, and PD-L1 and CTLA4 mRNA expression. Conclusions: In BTC, methylation patterns may serve as a robust indicator of immune-related features and prognosis. Our integrative analysis highlights the association between genomic and epigenomic features, and provides insights into the molecular heterogeneity, and the potential therapeutic significance in biliary tract malignancies. Included methylation sites in the LASSO model.[Table: see text]

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A retrospective cohort study of anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14100 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14100-e14100 ◽

Cited By ~ 1

Author(s):

Danyang Sun ◽

Junxun Ma ◽

Jinliang Wang ◽

Chun Han ◽

Yuanyu Qian ◽

...

Keyword(s):

Combination Therapy ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Treatment Options ◽

Progression Free Survival ◽

Immune Checkpoints ◽

Secondary Outcome ◽

Combination Group ◽

Tract Cancer ◽

Significant Difference

e14100 Background: Biliary tract cancer (BTC) is highly aggressive with poor prognosis and few treatment options following progression on gemcitabine-based chemotherapy. Disappointing results from clinical trials for refractory BTC highlight the need for more effective therapies. Immune checkpoint inhibitor (ICI) has been hailed as a major breakthrough for cancer treatment. However, evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. KEYNOTE-158 trial has merely shown a 5.8% of overall response rate with pembrolizumab monotherapy in advanced BTCs. Thus, combining other therapies with ICIs is becoming the researching focus. Herein, we constructed a cohort to evaluate the efficacy and safety of ICIs combined with chemotherapy in advanced BTCs. Methods: Chinese BTC patients receiving PD-1 inhibitors with chemotherapy, PD-1 inhibitors monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcome were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T-cell co-stimulation or immune checkpoints were excluded. Results: The study included 77 patients (PD-1 inhibitors plus chemotherapy, n = 38; PD-1 inhibitors monotherapy, n = 20; chemotherapy, n = 19). Median OS was 14.9 months with PD-1 inhibitors plus chemotherapy, 4.1 months with PD-1 inhibitors and 6.0 months with chemotherapy, with significantly longer for anti-PD-1 combination therapy than monotherapy (HR 0.37, 95% CI 0.17-0.80, P= 0.001) or chemotherapy (HR 0.63, 95% CI 0.42-0.94, P= 0.011). Median PFS was 5.1 months with PD-1 inhibitors plus chemotherapy, 2.2 months with PD-1 inhibitors and 2.4 months with chemotherapy, with significant difference for anti-PD-1 combination therapy versus anti-PD-1 monotherapy (HR 0.59, 95% CI 0.31-1.10, P= 0.014) or chemotherapy (HR 0.61, 95% CI 0.45-0.83, P= 0.003). Grade 3 or 4 treatment-related adverse events were similar between anti-PD-1 combination group and chemotherapy group (34.2% and 36.8%). Conclusions: PD-1 inhibitors plus chemotherapy is effective and tolerable for advanced BTC.

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