scholarly journals Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiyi Zhang ◽  
Xingyu Liu ◽  
Shumei Wei ◽  
Lufei Zhang ◽  
Yang Tian ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Objective Response ◽  
Pathologic Response ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
First Line Treatment

ObjectiveWe investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC).MethodsIn this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers.ResultsAmong 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6–11.4) and the median OS was 17.7 months (95% CI: not estimable).ConclusionsLenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated.Clinical Trial Registrationwww.chictr.org.cn, ChiCTR2100044476.

S-1 monotherapy as first-line treatment in patients with advanced biliary tract cancer: a multicenter phase II study

2008 ◽  
Vol 62 (5) ◽  
pp. 849-855 ◽  
Author(s):  
Junji Furuse ◽  
Takuji Okusaka ◽  
Narikazu Boku ◽  
Shinichi Ohkawa ◽  
Akira Sawaki ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
Multicenter Phase ◽  
First Line Treatment

scholarly journals Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

2018 ◽  
Vol 118 (7) ◽  
pp. 966-971 ◽  
Author(s):  
David K. Lau ◽  
Rebecca Y. Tay ◽  
Yvonne H. Yeung ◽  
Fiona Chionh ◽  
Jennifer Mooi ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
First Line Treatment

Phase II study of everolimus monotherapy as first-line treatment in advanced biliary tract cancer: RADichol.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 4101-4101 ◽  
Author(s):  
Yvonne H. Yeung ◽  
Fiona J.M. Chionh ◽  
Timothy Jay Price ◽  
Andrew Mark Scott ◽  
Hoanh Tran ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
First Line Treatment

scholarly journals Tumor Mutational Burden as a Biomarker for Advanced Biliary Tract Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110623
Author(s):  
Hongsik Kim ◽  
Hana Kim ◽  
Ryul Kim ◽  
Hyunji Jo ◽  
Hye Ryeon Kim ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
First Line Treatment

Background: High tumor mutational burden (TMB-H) has been reported as a predictive marker to immunotherapy or prognostic marker in various tumor types. However, there has been little study of the role of TMB-H in advanced biliary tract cancer (BTC). Methods: We analyzed 119 advanced BTC patients who received Gemcitabine/Cisplatin (GP) as a first-line treatment between November 2019 and April 2021. Next-generation sequencing (NGS), including TMB analysis, as a routine clinical practice was performed in 119 patients. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. Results: Among 119 patients, 18 (18.5%) had a tumor with high TMB (≥ 10 Muts/Mb). There were no significant differences between the status of TMB and clinical outcomes with GP, including objective response rate (ORR) ( P = .126), disease control rate (DCR) ( p = .454), and median progression-free survival (PFS) ( p = .599). The median overall survival (OS) was not different between patients with TMB-H and no TMB-H ( p = .430). In subgroup analysis of 32 patients receiving immune checkpoint inhibitor (ICIs), there were significant differences in ORR ( p = .034) and median PFS ( p  = .025) with ICIs between patients with and without TMB-H. Conclusions: This study revealed that TMB-H in advanced BTCs did not have a prognostic or role in the standard first-line treatment. However, TMB-H might be a predictive biomarker for response to ICIs in advanced BTC.

scholarly journals Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001240 ◽  
Author(s):  
Xiaofeng Chen ◽  
Xiaofeng Wu ◽  
Hao Wu ◽  
Yanhong Gu ◽  
Yang Shao ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Tract Cancer ◽  
Open Label Phase ◽  
First Line Treatment ◽  
Potential Biomarkers

BackgroundImmune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.MethodsIn this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.Results54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).ConclusionCamrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.Trial registration numberNCT03486678.

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