Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 225-225 ◽  
Author(s):  
Julien Edeline ◽  
Franck Bonnetain ◽  
Jean Marc Phelip ◽  
Jérôme Watelet ◽  
Pascal Hammel ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Post Surgery ◽  
Significant Difference ◽  
Grade 3

225 Background: No standard post-surgery adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Gemcitabine combined with platinum is the standard chemotherapy for advanced BTC. The aim of this phase III randomized trial was to assess whether GEMOX would increase relapse-free survival (RFS) while maintaining health-related quality of life (HrQoL). Methods: We performed a multicenter randomized phase III trial. Patients were randomized, within 3 months of R0 or R1 resection of a localized BTC (intra-hepatic, perihilar, extra-hepatic cholangiocarcinoma or gallbladder cancer), to receive either GEMOX 85 for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary objectives were RFS and HrQoL. 190 patients and 126 RFS events were required to show an increase of median RFS from 18 to 30 months. Results: Between July 2009 and February 2014, 196 patients were included in 33 French centers. Baseline characteristics were balanced, with similar primary sites, R0 resection rates were 86.2% (Arm A) vs 87.9% (Arm B), lymph node invasion present in 37.2% vs 36.4%. In Arm A, a median of 12 cycles was delivered (mean: 9.3, range: 0-12). Maximal grade of adverse events were grade 3 in 57.5% vs 22.2%, and grade 4 in 17.0% vs 9.1%. During treatment one patient died in each arm. The main grade ≥ 3 adverse events in the year following inclusion were peripheral neuropathy (50.0% vs 1.1%), and neutropenia (22.3% vs 0%). Median follow-up was 44.3 months, with 54 and 64 RFS events in arms A vs B. There was no significant difference in RFS between the arms (log-rank p = 0.31), with a hazard ratio of 0.83 [95% CI: 0.58-1.19], p = 0.31 (futility boundaries were crossed). Median RFS was 30.4 [95% CI: 15.4-45.8] vs 22.0 months [95%CI: 13.6-38.3] in arms A & B respectively, and 4-years RFS was 39.3% [95%CI: 28.4%-50.0%] vs 33.2% [95%CI: 23.1-43.7%]. Global Health HrQoL scores were not different at 12 months (70.8 vs 83.3, p = 0.18) and at 24 months (75.0 vs 83.3, p = 0.50). Conclusions: Adjuvant chemotherapy in BTC with GEMOX was feasible and associated with expected toxicities and no deterioration of HrQoL. There was no significant difference in RFS between GEMOX and surveillance. Clinical trial information: NCT01313377.

Randomized phase II trial of gemcitabine plus S-1 combination therapy versus S-1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 255-255 ◽  
Author(s):  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Junki Mizusawa ◽  
Atsuo Takashima ◽  
Makoto Ueno ◽  
...  
Keyword(s):  
Survival Time ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Correct Selection ◽  
Biliary Duct ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Subsequent Phase ◽  
Grade 3

255 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1000 mg/m2, iv, days 1 and 8; S-1: 60 mg/m2, p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m2, p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p<0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.

Randomized phase II trial of gemcitabine plus S−1 combination therapy versus S−1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4031-4031
Author(s):  
Makoto Ueno ◽  
Takuji Okusaka ◽  
Junki Mizusawa ◽  
Atsuo Takashima ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Survival Time ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Correct Selection ◽  
Biliary Duct ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Subsequent Phase ◽  
Grade 3

4031 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1,000 mg/m2, iv, days 1 and 8; S-1: 60 mg/m2, p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m2, p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p<0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.

Frequency of severe neutropenia occurring as an adverse events of gemcitabine plus cisplatin chemotherapy in patients with recurrent biliary tract cancer compared to those with unresectable biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 488-488
Author(s):  
Noriko Fujishiro ◽  
Shuichi Mitsunaga ◽  
Akira Shinohara ◽  
Misaki K Takeno ◽  
Hideki Funazaki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Intrahepatic Bile Duct ◽  
Severe Neutropenia ◽  
Primary Tumor Site ◽  
Tract Cancer ◽  
Significant Difference ◽  
Grade 3

488 Background: In patients (pts) with biliary tract cancer (BTC), relapse occurs at a high frequency even after curative resection. It remains unclear whether in pts with postoperative recurrence receiving chemotherapy, the surgery exerts any influence on the risk of development of toxicities. The aim of this study was to compare the outcomes and incidences of adverse events between recurrent BTC (rBTC) pts and unresectable BTC (uBTC) pts receiving gemcitabine plus cisplatin chemotherapy (GC). Methods: Data of pts with rBTC or uBTC receiving GC as the first-line chemotherapy were analyzed. The GC regimen consisted of gemcitabine 1000 mg/m2 plus cisplatin 25 mg/m2on days 1 and 8, administered every 3 weeks. All adverse events occurring during the first 180 days of GC were evaluated according to CTCAE, version 4.0. Results: A total of 151 pts, including 55 pts with rBTC and 96 pts with uBTC, were enrolled. In regard to the baseline characteristics, no significant differences between the rBTC and uBTC groups were found in the gender distribution [male: 69% vs. 57%], age [median: 68 vs. 68], or ECOG performance status (PS) [PS0: 67%vs. 55%]. The distribution of the primary tumor site (intrahepatic bile duct [27% vs. 33%] / extrahepatic bile duct [45% vs. 20%] / gallbladder [20% vs. 44%] / ampulla [7% vs. 3%]) was unbalanced between the two groups ( p < 0.01). The overall survival (OS) was significantly longer in the rBTC group than that in the uBTC group [median 15.8 months vs. 10.0 months, p = 0.02], however, there was no significant difference in the progression-free survival [median 6.8 months vs. 5.8 months] between the two groups. Grade 3-4 neutropenia was more frequent in the rBTC group [69%] as compared to that in the uBTC group [44%, p < 0.01], whereas Grade 3-4 cholangitis was significantly less frequent in the rBTC [5%] group than that in the uBTC group [21%, p = 0.02]. Conclusions: The incidence of Grade 3-4 neutropenia developing during GC was significantly higher in the rBTC group as compared to that in the uBTC group.

Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study

2019 ◽  
Vol 37 (8) ◽  
pp. 658-667 ◽  
Author(s):  
Julien Edeline ◽  
Meher Benabdelghani ◽  
Aurélie Bertaut ◽  
Jérôme Watelet ◽  
Pascal Hammel ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Open Label ◽  
Tract Cancer ◽  
R1 Resection ◽  
Significant Difference ◽  
Related Quality ◽  
Health Related ◽  
Grade 3

PURPOSE No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection. PATIENTS AND METHODS We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL. RESULTS Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001). CONCLUSION There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.

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.

scholarly journals A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01)

2020 ◽  
Author(s):  
Osamu Itano ◽  
Yusuke Takemura ◽  
Norihiro Kishida ◽  
Eiji Tamagawa ◽  
Hiroharu Shinozaki ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Disease Free Survival ◽  
Completion Rate ◽  
Inclusion Criteria ◽  
Tract Cancer ◽  
Post Surgery ◽  
One Year

Abstract Background: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial.Methods: The inclusion criteria were as follows: histologically proven BTC, ECOG performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1–28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS) and overall survival (OS).Results: Overall, 46 patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporal therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered S-1 more than 3 courses, only one case discontinued due to adverse events.Conclusions: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing.Trial registration: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347)

The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 368-368
Author(s):  
Makoto Ueno ◽  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Gakuto Ogawa ◽  
Yuya Sato ◽  
...  
Keyword(s):  
Renal Function ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Grade 3 ◽  
The Impact

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.

A pilot study of durvalumab/tremelimumab (durva/treme) and radiation (XRT) for metastatic biliary tract cancer (mBTC): Preliminary safety and efficacy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 547-547
Author(s):  
Theodore S. Hong ◽  
Lipika Goyal ◽  
Aparna Raj Parikh ◽  
Beow Y. Yeap ◽  
Christine A. Ulysse ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Control ◽  
Dose Level ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Single Agent ◽  
Safety And Efficacy ◽  
Tract Cancer ◽  
Level 1 ◽  
Grade 3

547 Background: Metastatic biliary tract cancer (mBTC) is a lethal malignancy with median 5 year OS of less than 10%. Immunotherapy, particularly single agent anti-PD-1/PD-L1, has limited efficacy in mBTC with ORR~9-15%. Recently presented data shows responses in metastatic MSS pancreatic or colon cancer with combination anti-PD-1/CTLA-4 and radiation (XRT) to produce systemic response (abscopal effect) (Parikh A, GI ASCO 2019, ASCO 2019.). We evaluate safety and efficacy of dual PD-1/CTLA-4 inhibition with XRT in MSS mBTC. Methods: 15 of a planned 15 mBTC patients were enrolled. Eligible pts had histologically-confirmed mBTC, ECOG-PS 0/1, and must have progressed on at least one line of previous therapy or refused standard therapy. Safety cohort of 6 pts of durva 1500 mg/treme 75 mg q4w was enrolled. If > 2 DLTs, patients were enrolled subsequently to dose level -1 (durva 1125 mg/ treme 75 mg q4w). 3 fractions of 8 Gy of radiation at C2D1 every other day to a single metastatic site. Durva/treme continued for 4 cycles, followed by 4 cycles of maintenance durva until progressive disease, discontinuation or withdrawal. Endpoints include disease control rate (DCR (SD+PR+CR)), PFS and OS and safety. Radiological evaluations were done q2 mo. Results: 15 mBTC pts enrolled and evaluable from May 2018 to March 2019. Median age 63 years (range 48-75), 47% male. DLTs occurred in 3 patients during the safety run-in. One patient experienced DLT at dose level -1 and subsequent expansion. 3 patients did NOT reach radiation therapy. DCR was 27% with a 13% PR and 7% CR. Of those who reached radiation, DCR was 33% with a 17% PR and 8% CR. At time of analysis, median PFS was 54 days for ITT mBTC. Duration of response for 4 patients with DCR was 26, 52, 122, 254+ days. Treatment-related adverse events were reported in 12/15 patients (80%). Grade ≥3 toxicities were seen in 9/15 pts (60%) with lymphopenia (5 grade 3) and elevated LFTs (2 grade 4 and 4 grade 2) being the main adverse events. All patients with disease control were not MSI. Conclusions: Combination of durva/treme XRT is feasible and shows preliminary activity in metastatic BTC. An expansion cohort is being planned to confirm activity. Clinical trial information: NCT03482102.

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