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 Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

2020 ◽  
Vol 52 (2) ◽  
pp. 594-603 ◽  
Author(s):  
Junho Kang ◽  
Jae Ho Jeong ◽  
Hee-Sang Hwang ◽  
Sang Soo Lee ◽  
Do Hyun Park ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Current Standard ◽  
Durable Response ◽  
Tract Cancer ◽  
Potential Biomarker

Purpose The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. Materials and MethodsIn this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. ResultsBetween May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

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

A phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 417-417
Author(s):  
Nai-Jung Chiang ◽  
Jen-Shi Chen ◽  
Ming-Huang Chen ◽  
Shih-Hung Yang ◽  
Chiun Hsu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Null Hypothesis ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standard Regimen ◽  
Tract Cancer ◽  
To Receive

417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m2 gemcitabine with 10 mg/m2/min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p0= 0.4, p1= 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD≥ 12weeks]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p0) would be rejected if 24 or more patients with CR/PR/SD≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD>12weeks. The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD≥ 12weeks, the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.

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.

Efficacy and safety of nivolumab in first-line or further treatment of advanced metastatic biliary tract cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 315-315
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Haiyan Si ◽  
Guanghai Dai
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Efficacy And Safety ◽  
Peripheral Neurotoxicity ◽  
Tract Cancer

315 Background: PD-1 inhibitors have improved efficacy in many cancers. There are few report of nivolumab for metastatic biliary tract cancer (MBTC). This study reviewed the efficacy and safety of nivolumab for MBTC to improve efficacy and survival. Methods: Thirty patients with MBTC were voluntarily treated with non-clinical nivolumab at the PLA General Hospital. Nivolumab 200 mg or 180 mg was administered according to patient tolerance. Progression free survival (PFS), overall survival (OS) was evaluated by kaplan-meier and univariate analysis were carried out among clinical characteristics. Objective response rates (ORR), disease control rates (DCR), and treatment-related adverse events (AEs) were also evaluated. Results: The median treatment cycle is 4 cycles. One case was complete response (CR), 5 cases partial response (PR), 12 cases stable (SD). ORR was 20%, DCR was 60%. PFS was 3.1m (95% CI: 2.13~4.06 months). The AEs of nivolumab monothrapy were fatigue (3 cases), fever (2 cases), hypothyroidism (1 case), skin reaction (1 case). Nivolumab combined with chemotherapy related 1-2 hematologic toxicity were leukopenia (5 cases), thrombocytopenia (2 cases), and grade 3-4 were leukopenia (3 cases). Non-hematologic toxicity grade 1-2 were nausea and vomiting (4 cases), fatigue (4 cases), fever (3 cases), peripheral neurotoxicity (3 cases), and hypothyroidism (1 case). Univariate analysis showed that PFS was 4.20m in patients older than 53 years, slightly higher than those younger than 53 years (3.0 m, P = 0.047). PFS of nivolumab combined with chemotherapy was statistically significant compared with nivolumab monothrapy (4.1 m vs 2.3 m, p = 0.031). Patients with metastatic number > 2 had a shorter PFS than those < 2 (1.4 m vs 4.1 m, P = 0.05). PD-L1 expression positive have no better PFS compared with PD-L1 negative (3.6 m vs 3.1 m , p = 0.801). Multivariate analysis show nivolumab combined with chemotherapy was only independent factor for longer PFS (HR: 0.432, P < 0.05). Conclusions: the safety of nivolumab in MBTC is controllable. Subgroup analysis suggests that further selection of superior populations is needed and sample size need to be expanded to improve the efficacy of nivolumab in MBTC.

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 Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial

2020 ◽  
Vol 122 (5) ◽  
pp. 634-639 ◽  
Author(s):  
Ali Belkouz ◽  
Judith de Vos-Geelen ◽  
Ron A. A. Mathôt ◽  
Ferry A. L. M. Eskens ◽  
Thomas M. van Gulik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Salvage Treatment ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Tract Cancer ◽  
Grade 3

Abstract Background No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage treatment in patients with previously treated advanced BTC. Methods In this two-stage phase 2 study, patients with advanced BTC who had disease progression or unacceptable toxicity after ≥3 cycles of GEMCIS were eligible. Primary endpoints were safety and efficacy (defined as objective response rate, ORR). In stage one, ten patients were treated with FOLFIRINOX every 2 weeks. In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results Forty patients were screened for eligibility and 30 patients were enrolled. In stage one, one patient had a partial response and five patients had stable disease. One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events. The most common grade 3–4 adverse events in stage one were neutropaenia, mucositis and diarrhoea. Stage two was initiated with FOLFIRINOX in an adapted dose. In stage two, grade 3–4 neutropaenia, diarrhoea, nausea and vomiting were the most common adverse events. The ORR, median PFS and OS in all patients were 10%, 6.2 and 10.7 months, respectively. Conclusions In patients with advanced BTC who progressed after or were intolerant to GEMCIS, FOLFIRINOX can be administered safely and could be considered as an option for salvage treatment in these patients. Clinical trial registration ClinicalTrials.gov Identifier NCT02456714.

A prospective randomized controlled trial comparing 4-weekly versus 3-weekly adjuvant chemotherapy with gemcitabine after curative resection of biliary tract cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 345-345
Author(s):  
Shin Nakahira ◽  
Shogo Kobayashi ◽  
Atsushi Miyamoto ◽  
Junzo Shimizu ◽  
Masaki Kashiwazaki ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Controlled Trial ◽  
Survival Rates ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Tract Cancer ◽  
Dose Modifications

345 Background: Resection of biliary tract cancer, employing pancreatoduodenectomy and major hepatectomy, is highly aggressive. Thus, postoperative gemcitabine cannot be administered employing a routine dosage protocol. We theorized that a 3-weekly protocol (days 1 and 8, every 3 weeks) of gemcitabine as adjuvant chemotherapy would be superior to the usually administered 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Methods: The outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol were compared in a prospective randomized clinical setting. The primary endpoint was the treatment completion rate, while secondary endpoints were adverse events and recurrence-free survival. Results: We enrolled a total of 27 patients. Only two patients (14%) on the 4-weekly protocol and three (23%) on the 3-weekly protocol (p=0.8099) completed treatment with no omissions and/or dose modifications. Most of the remaining patients (70%) experienced grade 3/4 neutropenia. Relative dose intensities were 72% and 78%, respectively, with the 4-weekly and 3-weekly protocols. Recurrence-free survival rates did not differ significantly between the two protocols. Conclusions: Contrary to our hypothesis, the 3-weekly protocol did not produce superior results in terms of completion, adverse events or recurrence-free survival rates as compared to the standard 4-week protocol.

Impact of sex on outcomes and adverse events in the advanced biliary tract cancer (ABC)-01 to -04 studies.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16131-e16131
Author(s):  
John A. Bridgewater ◽  
Andre Lopes ◽  
Anna Dorothea Wagner ◽  
Juan W. Valle
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
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.

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