Cisplatin plus irinotecan in the treatment of gallbladder or biliary tract cancer: A randomized phase II trial (NCT01859728).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS485-TPS485
Author(s):  
Lucas Vieira dos Santos ◽  
MauriÂcio Wagner Souto Ferraz ◽  
Joao Paulo Lima ◽  
Kathia Cristina Abdalla
Keyword(s):  
Clinical Trial ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Ampulla Of Vater ◽  
Metastatic Carcinoma ◽  
Tract Cancer ◽  
Institutional Review ◽  
Platinum Chemotherapy

TPS485 Background: Gallbladder and biliary tract cancer (GBTC) have an aggressive behavior and gemcitabine-platinum chemotherapy emerged as the new standard of care for advanced or metastatic GBTC. Despite optimal management, prognosis is still poor. This randomized trial aims to compare irinotecan plus cisplatin versus gembitabine plus cisplatin in advanced or metastatic GBTC. Methods: Patients with biopsy-proven, chemo-naïve, unresectable or metastatic carcinoma of GBTC (gallbladder, intrahepatic biliary tract, extrahepatic biliary tract, or ampulla of Vater), ECOG 0-2, measurable disease per RECIST 1.1, adequate organ function and written informed consent are stratified by ECOG (0 or 1 vs 2) and hematogenic metastases (yes vs no) and randomized to receive Irinotecan 65mg/m² D1 and D8 q21 days plus Cisplatin 60mg/m² D1 q 21 days (IP) or Gemcitabine 1000mg/m² D1 and D8 every 21 days plus cisplatin 25mg/m² D1 and D8 every 21 days (GC), until disease progression or unacceptable toxicity, with standard hydration and antiemetics. Computed tomography for response evaluation is undertaken every 6 weeks. The primary end-point is overall response rate (ORR). Assuming p0 = 25%, p1 = 50%, alpha = 5% and beta = 20% in an optimal Simon’s two stage design, 24 patients per arm will be recruited (N1 = 9; R1 = 2; Ntot = 24; Rtot = 9). The sample size for each arm was calculated separately. Secondary end-points are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), quality of life and safety. This clinical trial was activated in January 2013 and the accrual period is expected to end by December 2017. This protocol was approved by institutional review board. Clinical trial information: NCT01859728.

Cisplatin plus irinotecan versus cisplatin plus gemcitabine in the treatment of advanced or metastatic gallbladder or biliary tract cancer: Results of a randomized phase II trial (NCT01859728)– the Gambit trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 529-529
Author(s):  
Lucas Vieira dos Santos ◽  
Gustavo Sanches Faria Pinto ◽  
Mauricio Wagner Souto Ferraz ◽  
Arinilda Bragagnoli ◽  
Florinda Santos ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Complete Response ◽  
Current Standard ◽  
Tract Cancer ◽  
To Receive

529 Background: The combination of gemcitabine-cisplatin (GC) is the current standard of care chemotherapy for metastatic/unresectable biliary tract cancer (BTC). However, the prognosis remains poor. This randomized trial aimed to evaluate the efficacy and safety of irinotecan plus cisplatin (IP) versus GC in advanced or metastatic BTC. Methods: Patients with biopsy-proven, chemo-naïve, unresectable or metastatic BTC, ECOG 0-2, measurable disease per RECIST 1.1, adequate organ function and written informed consent were stratified by ECOG (0 or 1 vs 2) and distant metastases and randomized to receive irinotecan 65 mg/m² IV D1 and D8 plus cisplatin 60 mg/m² D1 repeated every 3 weeks (IP) or gemcitabine 1000 mg/m² IV D1 and D8 plus cisplatin 25 mg/m² IV D1 and D8 repeated every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results: Between January 2013 and April 2018, 47 pts were randomized (1:1) to receive IP (N = 24) or GC (N = 23). Overall, groups were well balanced according to prognostic factors. The ORR was 35% (complete response 5%, partial response 30%) and 31.8% in IP and GC arms, respectively. Median progression-free survival were 5.3 vs 7.8 months (HR = 1.165, 95%CI 0.628-2.161, p = 0.628) and median overall survival were 11.9 and 9.8 months (HR = 0.859, 95%CI 0.431 – 1.710, p = 0.665) for IP and GC, respectively. Adverse events were not statistically different between arms, and results were consistent with previous experiences with these regimens. No therapy-related death were reported. Conclusions: Irinotecan-cisplatin combination is active in BTC, with similar ORR, PFS and OS when compared to gemcitabine-cisplatin. Irinotecan-cisplatin were well tolerated, and adverse events were manageable. Irinotecan-cisplatin could be considered as an alternative to gemcitabine-cisplatin. Clinical trial information: NCT01859728.

scholarly journals Investigator initiated clinical trial of cancer vaccine OCV-C01 in advanced and recurrent biliary tract cancer

2018 ◽  
Vol 29 ◽  
pp. vii60
Author(s):  
Mutsunori Murahashi ◽  
Hisanobu Ogata ◽  
Toshihiko Okazaki ◽  
Yasuki Hijikata ◽  
Kazunari Yamada ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Biliary Tract ◽  
Cancer Vaccine ◽  
Biliary Tract Cancer ◽  
Tract 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.

Pharmacotherapeutic options for biliary tract cancer: current standard of care and new perspectives

2019 ◽  
Vol 20 (17) ◽  
pp. 2121-2137 ◽  
Author(s):  
Roberto Filippi ◽  
Pasquale Lombardi ◽  
Virginia Quarà ◽  
Elisabetta Fenocchio ◽  
Giacomo Aimar ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Standard Of Care ◽  
Current Standard ◽  
Tract Cancer

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.

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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