scholarly journals The Efficacy and Safety of Apatinib Treatment for Patients with Advanced or Recurrent Biliary Tract Cancer: A Retrospective Study

2020 ◽  
Author(s):  
Caiyun Nie ◽  
Huifang Lv ◽  
Yishu Xing ◽  
Beibei Chen ◽  
Weifeng Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Tract Cancer ◽  
Systemic Therapies

Abstract Background The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer(BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy, including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. 6 patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months(95%CI = 1.8–6.8) and 6.2 months(95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

scholarly journals The efficacy and safety of apatinib treatment for patients with advanced or recurrent biliary tract cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caiyun Nie ◽  
Huifang Lv ◽  
Yishu Xing ◽  
Beibei Chen ◽  
Weifeng Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Tract Cancer ◽  
Systemic Therapies

Abstract Introduction The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8–6.8) and 6.2 months (95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

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 TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huanhuan Yin ◽  
Wei Guo ◽  
Xiangling Sun ◽  
Ruili Li ◽  
Cuihua Feng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Survival Time ◽  
Response Rate ◽  
Multivariate Analyses ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

Genomics and translational precision oncology for 803 patients with biliary tract cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4589-4589
Author(s):  
Jianzhen Lin ◽  
Xu Yang ◽  
Yinghao Cao ◽  
Guangyu Li ◽  
Songhui Zhao ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Targeted Therapies ◽  
Objective Response ◽  
Disease Free Survival ◽  
Tumor Board ◽  
Precision Oncology ◽  
Free Survival ◽  
Tract Cancer ◽  
Incidence And Mortality

4589 Background: Both incidence and mortality of biliary tract cancer (BTC) are increasing, and BTCs are characterized by poor prognosis and limited antitumoral treatments. There is no well-received regimen as the non-first-line treatment in patients with advanced BTCs, leading to the urgency of umbrella-setting personalized therapies according to genomic alterations. Methods: We performed genomic sequencing in a total of 803 BTCs, including 160 patients with whole-exome sequencing and 643 patients with hybrid capture–based comprehensive genomic profiling. Our molecular tumor board developed precise targeted therapies for patients with actionable targets. Results: Overall, the median tumor mutation burden was 3.0 (IQR: 0.8-6.1) Mut/Mb, with 10.5% patients of hypermutated BTCs. The most frequently mutated genes included TP53 (51%), KRAS (23%), ARID1A (16%) and SMAD4 (11%). The most common genes with significantly amplified oncogenes were CCND1 (6.97%), MET (6.72%) and MDM2 (6.6%), while the frequently deleted tumor-suppressor genes are CDKN2A (5.73%) and CDKN2B (5.35%). The mutational map of BTCs highlighted pathways of receptor-tyrosine kinase (RTK)/RAS and p53 signaling were frequently altered. Somatic truncating mutations of mismatch repair genes were identified in 6.1% (49/803) of patients, and germline pathogenic mutations in DNA damage response genes occurred in 8% (64/803) of BTCs. In addition, we demonstrate the amplified chromosomal focal at 7q31.2 was an oncogenic factor and it independently predicts both disease-free survival and overall survival of BTC patients. When molecular screening was linked to targeted therapies, 25.4% (204/803) of patients could match biomarker-assigned drug treatment (BADT). The frequent actionable biomarkers included amplifications of ERBB2 and MET, FGFR2/3 fusions and IDH1 mutations. For 46 patients with refractory BTCs received BADT, the objective response rate was 26.1%, with a median progression-free survival (mPFS) of 5.0 (95%CI: 3.5-6.5) months, and 56.8% patients achieved a ≥1.3 ratio of PFS2/PFS1. 4 of 6 (67%) patients with high microsatellite instability (MSI-H) BTCs had a responsive status after immunotherapy of PD1 inhibitor, confirming that MSI-H status was a robust biomarker of anti-PD1 treatments. Conclusions: Our study established the largest cohort in Chinese BTC patients to investigate the tumor mutational profiling and its translational clinical applications. Clinical trial information: NCT02715089 .

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 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.

scholarly journals Anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer

2019 ◽  
Vol 68 (9) ◽  
pp. 1527-1535 ◽  
Author(s):  
Danyang Sun ◽  
Junxun Ma ◽  
Jinliang Wang ◽  
Chun Han ◽  
Yuanyu Qian ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Primary Outcome ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Combination Group ◽  
Free Survival ◽  
Tract Cancer ◽  
Previously Treated ◽  
Grade 3

Abstract Background Evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. Methods Chinese BTC patients receiving a PD-1 inhibitor with chemotherapy, PD-1 inhibitor monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcomes were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T cell costimulation or immune checkpoints were excluded. Results The study included 77 patients (a PD-1 inhibitor plus chemotherapy, n = 38; PD-1 inhibitor monotherapy, n = 20; chemotherapy alone, n = 19). The median OS was 14.9 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 4.1 months with PD-1 inhibitor monotherapy (HR 0.37, 95% CI 0.17–0.80, P = 0.001) and the 6.0 months with chemotherapy alone (HR 0.63, 95% CI 0.42–0.94, P = 0.011). The median PFS was 5.1 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 2.2 months with PD-1 inhibitor monotherapy (HR 0.59, 95% CI 0.31–1.10, P = 0.014) and the 2.4 months with chemotherapy alone (HR 0.61, 95% CI 0.45–0.83, P = 0.003). Grade 3 or 4 treatment-related adverse events were similar between the anti-PD-1 combination group and the chemotherapy alone group (34.2% and 36.8%, respectively). Conclusions Anti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC.

scholarly journals Treatment of Patients with Advanced Biliary Tract Cancer with Either Oxaliplatin, Gemcitabine, and Capecitabine or Cisplatin and Gemcitabine—A Randomized Phase II Trial

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1975
Author(s):  
Alice Markussen ◽  
Lars Henrik Jensen ◽  
Laura Vittrup Diness ◽  
Finn Ole Larsen
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Tract Cancer ◽  
Randomized Phase Ii

This study is an investigator-initiated randomized phase II trial focusing on the treatment of advanced biliary tract cancer with either oxaliplatin 50 mg/m2 and gemcitabine 1000 mg/m2 on day 1 in a two-week cycle with capecitabine 650 mg/m2 twice-daily continuously or cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8 in a three-week cycle. One-hundred patients were included. Forty-seven patients received oxaliplatin, gemcitabine, and capecitabine with a median progression-free survival (mPFS) of 5.7 months (95% CI 3.0–7.8) and a median overall survival (mOS) of 8.7 months (95% CI 6.5–11.2). Forty-nine patients received cisplatin and gemcitabine with a mPFS of 7.3 months (95% CI 6.0–8.7) and a mOS of 12.0 months (95% CI 8.3–16.7). This trial confirms a mOS of 12 months with cisplatin and gemcitabine, as found in earlier trials. With a superior tumor control rate of 79% vs. 60% (p = 0.045), a difference in the mPFS of 1.6 months (HR = 0.721, p = 0.1), and a difference in the mOS of 3.3 months (HR = 0.731, p = 0.1), cisplatin and gemcitabine should still be considered the standard first-line treatment for advanced biliary tract cancer.

scholarly journals NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121)

2020 ◽  
Vol 16 (16) ◽  
pp. 1069-1081 ◽  
Author(s):  
Mairéad Geraldine McNamara ◽  
Lipika Goyal ◽  
Mark Doherty ◽  
Christoph Springfeld ◽  
David Cosgrove ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Resistance Mechanisms ◽  
Ampullary Cancer ◽  
Cancer Resistance ◽  
Tract Cancer ◽  
Patient Reported

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients ≥18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma, gallbladder or ampullary cancer); randomized (1:1) to NUC-1031 (725 mg/m2)/cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2)/cisplatin (25 mg/m2), on days 1/8, Q21-days. Primary objectives are overall survival and objective response rate. Secondary objectives: progression-free survival, safety, pharmacokinetics, patient-reported quality of life and correlative studies. (Investigational new drug (IND) number: 139058, European Clinical Trials database: EudraCT Number 2019-001025-28, ClinicalTrials.gov identifier: NCT04163900).

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