Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Hyera Kim ◽  
Jinchul Kim ◽  
Seonggyu Byeon ◽  
Kee-Taek Jang ◽  
Jung Yong Hong ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Extrahepatic Cholangiocarcinoma ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death ◽  
Combined Positive Score

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 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. Patients and 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 positivity. Results: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 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. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC 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 who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. Conclusion: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

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.

scholarly journals Efficacy and Safety of Pembrolizumab for Gemcitabine/Cisplatin-Refractory Biliary Tract Cancer: A Multicenter Retrospective Study

2020 ◽  
Vol 9 (6) ◽  
pp. 1769 ◽  
Author(s):  
Sang Hoon Lee ◽  
Hee Seung Lee ◽  
Sang Hyub Lee ◽  
Sang Myung Woo ◽  
Dong Uk Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Progression Free Survival ◽  
Cancer Type ◽  
Extrahepatic Cholangiocarcinoma ◽  
Tract Cancer ◽  
Tertiary Hospitals ◽  
Melanoma Treatment

Pembrolizumab, an anti-programmed cell death (PD)-1 monoclonal antibody, is an anticancer agent showing substantial benefit in lung cancer and melanoma treatment. Biliary tract cancer (BTC) has been shown to respond to pembrolizumab; however, no credible data of such treatment outcomes exist. Therefore, we assessed the clinical outcomes and safety of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC. In this multicenter study, we retrospectively analyzed 51 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC treated with pembrolizumab in four tertiary hospitals in Korea. PD-L1 positivity was defined as the expression of PD-L1 in ≥1% of tumor cells based on immunohistochemical staining (22C3, SP263, and E1L3N assays). The median age of the patients was 66 (range, 43–83) years and 29 (56.9%) were male. Extrahepatic cholangiocarcinoma was the most common cancer type (n = 30, 58.8%). Partial response and stable disease were achieved in 5 (9.8%) and 13 (25.5%) patients, respectively. Median progression-free survival and overall survival were 2.1 (95% CI, 1.7–2.4) and 6.9 (95% CI, 5.4–8.3) months, respectively. Overall, 30 (58.8%) patients experienced treatment-related adverse events (AEs). Only four (7.8%) patients experienced grades 3 and 4 AEs. In PD-L1-positive gemcitabine/cisplatin-refractory BTC, pembrolizumab presented durable efficacy, with a 9.8% response rate and manageable toxicity.

scholarly journals Prognostic role of programmed death-ligand 1 expression in patients with biliary tract cancer: a meta-analysis

Aging ◽  
2019 ◽  
Vol 11 (24) ◽  
pp. 12568-12580
Author(s):  
Changjiang Lei ◽  
Xiulan Peng ◽  
Xiaojun Gong ◽  
Ying Fan ◽  
Shenglin Wu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death

The prognostic role of soluble transforming growth factor-β (sTGFb) and soluble programmed death-ligand 1 (sPDL1) in biliary tract cancer patients treated with binimetinib and capecitabine.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 257-257
Author(s):  
Jin Won Kim ◽  
Kyung-Hun Lee ◽  
Ji-Won Kim ◽  
Koung Jin Suh ◽  
Ah-Rong Nam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Positive Correlation ◽  
Tract Cancer ◽  
Programmed Death

257 Background: Transforming growth factor (TGF) -β signaling is important for tumor growth and metastasis in biliary tract cancer (BTC). TGF-β attenuates tumor response to programmed death-ligand 1 (PD-L1) blockade. This study aimed to evaluate a correlation between soluble TGF-β (s TGF-β) and soluble PD-L1 (sPD-L1) and its prognostic role in BTC. Methods: Study population consisted of 34 patients enrolled in phase Ib clinical trial of binimetinib (MEK inhibitor) with capecitabine in gemcitabine-pretreated BTC (ClinicalTrials.gov: NCT02773459). Blood samples at screening, after first cycle, after second cycle, and at disease progression were prospectively collected. Plasma sTGF-β and sPD-L1 values were measured by using an enzyme-linked immunosorbent assay. Results: In total 34 patients, 25 (73.5%) and 9 patients (26.5%) were second-line and third-line setting, respectively. Median progression-free survival (PFS) and overall survival (OS) were 4.1 and 7.8 months. The mean baseline sTGF-β and sPD-L1 were 18.7 ng/ml and 3.1 ng/ml. There was a positive correlation between sTGF-β and sPD-L1 value (pearson correlation = 0.596, p < 0.001). Mean baseline value was likely to be higher in best response of progressive disease, followed by stable disease and partial response. Similarly, higher baseline sTGF-β showed significantly shorter PFS (3.4 vs 5.1 months (m), p = 0.047) and OS (5.4 vs 9.7 m, p = 0.042). Higher baseline sPD-L1 also had a trend for poor PFS and OS (PFS: 3.0 vs 4.3 m, p = 0.220; OS: 6.4 vs 9.7 m, p = 0.140). Regarding changes from baseline to after first cycle, sTGF-β change of > 3.6 ng/ml demonstrated significantly shorter OS (5.9 vs 10.8 m, p = 0.020), although PFS did not differ according to sTGF-β change (p = 0.210). In contrast, OS did not differ according to sPD-L1 change (p = 0.190). sPD-L1 change > -1.7 ng/ml even had longer PFS (5.1 vs 2.2 m, p = 0.005). Conclusions: In BTC patients with binimetinib and capecitabine, there is a positive correlation between sTGF-β and sPD-L1 value and higher baseline sTGF-β and sPD-L1 indicate a worse prognosis. The early change of sTGF-β and sPD-L1 during treatment could predict the survival.

scholarly journals Dual HER2 Blockade: An Emerging Option in Metastatic Biliary Tract Cancer?

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1301
Author(s):  
Angela Dalia Ricci ◽  
Alessandro Rizzo
Keyword(s):  
Gallbladder Cancer ◽  
Biliary Tract ◽  
Intrahepatic Cholangiocarcinoma ◽  
Biliary Tract Cancer ◽  
Heterogeneous Group ◽  
Perihilar Cholangiocarcinoma ◽  
Extrahepatic Cholangiocarcinoma ◽  
Tract Cancer ◽  
Hepatobiliary Malignancies

Biliary tract cancer (BTC) includes a heterogeneous group of aggressive and rare hepatobiliary malignancies, including gallbladder cancer, ampullary carcinomas, intrahepatic cholangiocarcinoma (iCCA), and extrahepatic cholangiocarcinoma, further subclassified into distal (dCCA) and perihilar cholangiocarcinoma (pCCA) [...]

Prognostic factors in advanced biliary tract cancer treated with first-line chemotherapy with cisplatin and gemcitabine.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 350-350
Author(s):  
Renata D'Alpino Peixoto ◽  
Daniel John Renouf ◽  
Howard John Lim
Keyword(s):  
Prognostic Factors ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Primary Tumor ◽  
Advanced Disease ◽  
Tumor Location ◽  
Primary Tumor Location ◽  
Tract Cancer ◽  
Ecog Ps ◽  
Line Chemotherapy

350 Background: Data regarding prognostic factors in advanced biliary tract cancer (ABTC) remains scarce. The aim of this study was to review our experience in ABTC as well as to evaluate potential prognostic factors for overall survival (OS) as defined in the ABC-02 trial. Methods: 106 consecutive patients with ABTC who initiated palliative chemotherapy with Cisplatin and Gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using our pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). Results: 106 patients (46 males) with a median age of 64 years (range 43 – 88) were included. Median progression free-survival (PFS) was 6.2 months (95%CI: 5.4-7.0). Median OS from diagnosis of advanced disease to death was 12.9 months (95%CI: 10.0-15.7), while median OS from initiation of chemotherapy to death was 10.0 months (95%CI: 7.3-12.6). 34.9% of the patients received 2nd line chemotherapy, with single-agent 5-fluorouracil being the most used drug. On univariate analysis, ECOG performance status (PS) at diagnosis, primary tumor location (gallbladder, intra-hepatic cholangiocarcinoma, extra-hepatic cholangiocarcinoma, ampulla of Vater, unkown), and sites of advanced disease (unresectable locally advanced, regional lymph nodes, liver-limited metastases, extra-hepatic metastases) were significantly associated with worse OS (p < 0.001, 0.003 and 0.009, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, prior stent and prior surgery were not significantly associated with OS. On multivariate analysis, predictors of poorer OS were ECOG PS (p<0.001), primary location (p=0.009), site of advanced disease (p=0.006) and CEA (p=0.002). Conclusions: In this population based analysis, outcomes for patients with ABTC were comparable to those noted in the ABC-02 trial. ECOG PS, primary tumor location, site of advanced disease and CEA were all found to be significantly prognostic.

Clinical benefit of maintenance therapy for patients with advanced biliary tract cancer without progression on first-line gemcitabine plus cisplatin.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 357-357
Author(s):  
Jaewon Hyung ◽  
Changhoon Yoo ◽  
Kyu-Pyo Kim ◽  
Bum Jun Kim ◽  
Jae Ho Jeong ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Clinical Benefit ◽  
Medical Center ◽  
Progression Free Survival ◽  
Observation Group ◽  
First Line ◽  
Tract Cancer ◽  
Maintenance Group

357 Background: Gemcitabine plus cisplatin (GP) is the standard first line chemotherapy for patients with advanced biliary tract cancer (BTC). In the pivotal ABC-02 study, patients received up to 24 weeks (6-8 cycles) of three-weekly GP. In daily practice setting, however, patients without progression often receive GP more than 6-8 cycles. It is uncertain whether maintenance treatment has clinical benefit in patients without progression on GP. Methods: Advanced BTC patients treated with GP between April 2010 and February 2015 in Asan Medical Center, Seoul, Korea, were retrospectively analyzed. Among the patients who did not progressed and stopped GP after 6-8 cycles, patients were stratified according to the further treatment; those with or without further cycles of GP (maintenance group vs observation group). Primary endpoint was overall survival (OS). Results: Among 740 patients, 231 patients (31.2%) were eligible for this analysis; 111 for observation group, 120 for maintenance group. In observation group, 76 patients (68.5%) stopped GP due to completion of scheduled chemotherapy and 27 patients (24.3%) due to the patients’ request or toxicity. There were no statistically significant differences in baseline characteristics between two groups. Median OS from the initiation of GP was 20.5 months [95% CI 15.4-25.6] and 22.4 months [95% CI 17.0-27.8] in the observation and maintenance group, respectively (p = 0.32). Median progression-free survival (PFS) was 10.4 months [95% CI 7.0-13.8] and 13.2 months [95% CI 11.3-15.2], respectively (p = 0.22). These were consistent in the multivariate analyses for OS and PFS after the adjustment of prognostic factors. Conclusions: In our analysis, maintenance therapy of GP was not associated with improved survival outcomes. Considering the potential disadvantages such as cumulative toxicities, maintenance therapy may not be beneficial in patients who did not progressed on 6-8 cycles of GP.

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