scholarly journals PD-1 Inhibitors Could Improve the Efficacy of Chemotherapy as First-Line Treatment in Biliary Tract Cancers: A Propensity Score Matching Based Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Tiee Liu ◽  
Haiyan Si ◽  
Zhikuan Wang ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Biliary Tract ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Extrahepatic Bile Duct Cancer ◽  
Biliary Tract Cancers ◽  
Grade 3 ◽  
First Line Treatment

BackgroundThere are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC.MethodsWe retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan–Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed.ResultsThis study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%).ConclusionsAnti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.

scholarly journals An Assessment of Combination of the Camrelizumab With Chemotherapy in Metastatic Biliary Tract Cancers

2021 ◽  
Vol 28 ◽  
pp. 107327482110171
Author(s):  
Yi Yu ◽  
Shanshan Huang ◽  
Jun Chen ◽  
Feng Yu ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Biliary Tract ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Biliary Tract Cancers ◽  
Grade 3 ◽  
First Line Treatment

Background: Monoclonal antibodies that target the PD-1 receptor are emerging as promising therapeutic candidates for the treatment of biliary tract cancers (BTCs). The purpose of the current study was to assess the combination of the camrelizumab with chemotherapy as a first-line treatment for metastatic BTCs. Methods: We conducted a prospective single-arm pilot study of PD-1 antibody (camrelizumab 3 mg/kg d1, Q2 W or Q3 W) combined with different chemotherapy regimens as first-line treatment for BTCs. Efficacy endpoints were objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Treatment-related adverse events (TRAEs) were also evaluated. Results: Fourteen patients with histologically confirmed BTCs were evaluated. The ORR was 14.3% (95% CI: 1.8 to 42.8) and the DCR was 64.3% (95%CI: 41.7 to 86.9). The median PFS was 6.5 months (95% CI: 3.8 to 9.2), and the 6- and 12-month PFS rates were 61.6% and 12.3%, respectively. The median OS was 9.9 months (95% CI: 7.6 to 12.2), and the 6-and 12-month OS rates were 74.5% and 26.6%, respectively. All patients displayed at least 1 TRAE., and Grade 3 or 4 TRAEs occurred in 6 (42.86%) patients. Conclusions: Camrelizumab combined with chemotherapy as first-line treatment for metastatic BTCs demonstrated acceptable safety and efficacy in our pilot study. These findings warrant prospective controlled clinical trials comparing combinations of camrelizumab and chemotherapy to standard regimens.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14604-e14604
Author(s):  
Xiaodong Zhang ◽  
Ming Lu ◽  
Jifang Gong ◽  
Jing Gao ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Treatment Plan ◽  
Cell Cancer ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

e14604 Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR >60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.

SHR-1210 combined with GEMOX as first-line treatment in patients with advanced biliary tract cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 535-535 ◽  
Author(s):  
Xiaofeng Chen ◽  
Xiaofeng Wu ◽  
Hao Wu ◽  
Qianwen Shao ◽  
Feipeng Zhu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Biliary Tract Cancer ◽  
Combined Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Tract Cancer ◽  
Grade 3 ◽  
First Line Treatment

535 Background: This study aimed to evaluate the efficacy and safety of SHR-1210 (a humanized anti-programmed cell death receptor 1 antibody) plus gemcitabine and oxaliplatin (GEMOX) as first line treatment in patients (pts) with biliary tract cancer (BTC). Methods: This was a single-arm, single-center, exploratory trial, which included advanced BTC pts. Pts received SHR-1210 (3mg/kg, total dose ≤200mg, ivd, D1/2W) combined with gemcitabine (800 mg/m2, ivd, D1/2W) and oxaliplatin (85mg/m2, ivd, D2/2W). Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take SHR-1210 as single agent until disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS) rate. Results: From February 2018 to April 2019, 37 eligible pts were enrolled. The median age was 64 (range 41-74) years, male/female was 70.3/29.7%, and bile duct cancer/gallbladder cancer was 59.5/40.5%. All 37 pts were included in the safety analysis. The overall AE incidence rate was 97.3%. The incidence of grade ≥3 AEs was 73.0%, which mainly included increased GGT (gammaglutamyltransferase, 18.9%), hypokalemia (18.9%), and fatigue (16.2%). Particularly, the incidence of fever is 73.0%, in which 2 pts experienced grade 3/4 fever. Among 36 evaluable pts, 19 pts got partial response (PR, 52.8%), 14 pts stable disease (SD, 38.9%), and 3 pts progressive disease (PD, 8.3%) at best. The primary endpoint 6-month PFS rate was 50.0% (95% CI 32.4-65.4), which indicated that the primary endpoint of the study was reached, and mPFS was 6.2 months (95% CI 4.2-7.1). The 12-month overall survival (OS) rate was 50.5% (95% CI 30.6-67.4), and mOS was 12.1 months (95% CI 8.0-NA). Conclusions: This study has reached the pre-defined primary endpoint with a high response rate. Predictive biomarker analysis was reported in another abstract. Further study is needed to validate the efficacy of this combination. Clinical trial information: NCT03486678.

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.

Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma: A phase 2 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4089-4089
Author(s):  
Yongkun Sun ◽  
Ai-Ping Zhou ◽  
Wen Zhang ◽  
Lin Yang ◽  
Chengxu Cui ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Gallbladder Carcinoma ◽  
Tumor Location ◽  
Line Treatment ◽  
Phase 2 ◽  
First Line ◽  
Extrahepatic Cholangiocarcinoma ◽  
Common Grade ◽  
Grade 3 ◽  
First Line Treatment

4089 Background: Gemcitabine plus cisplatin or S-1 can be used as first-line treatment for advanced or metastatic biliary tract adenocarcinoma. Multiple phase 2 studies found that gemcitabine, oxaliplatin, capecitabine, S-1 were not superior to gemcitabine plus cisplatin. Nab-paclitaxel plus S-1 was effective and well-tolerated in pancreatic cancer. Methods: Patients with pathological confirmed advanced or metastatic biliary tract adenocarcinoma (gallbladder carcinoma, intrahepatic cholangiocarcinoma ICC, extrahepatic cholangiocarcinoma ECC) were treated with Nab-paclitaxel plus S-1(Nab-paclitaxel 120mg/m2, d1 and d8; S-1 80-120mg/d, d1-14; q21d). Patients that received PR or SD (RECIST1.1)after 6 cycles were given S-1 maintenance treatment. The primary endpoint was ORR. The study used Simon’s Two Stage design. Results: From March 2016 to September 2018, we recruited 54 patients, with 27 males (50%). The median age was 58(34-73yrs). As of Dec 31 2018, the median treatment cycle was 4(1-6 cycles). 51 patients were evaluable for efficacy: PR 14(27.5%), SD 22 (DCR=PR+SD: 70.6%), PD 15 (29.4%). The median PFS was 6 months, and the median OS was 13.2 months. The response rate varied in different tumor location: gallbladder carcinoma 53.8% (7/13), ICC 18.2% (6/33), ECC 20% (1/5).Common grade 3/4 AEs were: leucopenia 17 (31.5%), hyperbilirubinemia 5(9.3%), Mucositis 4 (7.4%), neurotoxicity 2 (3.7%), diarrhea 2 (3.7%), omit 1(1.9%), fatigue 1 (1.9%), thrombocytopenia 1 (1.9%), ALT increase 1 (1.9%). Conclusions: Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma was effective and well-tolerated, especially for gallbladder carcinoma (ORR 53.8%). This regimen need further exploration. Clinical trial information: NCT03830606.

scholarly journals Efficacy and Safety of Docetaxel Plus Oxaliplatin and Capecitabine in the First Line Treatment of Advanced Gastric Adenocarcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Ying Liu ◽  
Zhengbao Ye ◽  
Wenqi Xi ◽  
Tao Ma ◽  
Min Shi ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Large Scale ◽  
Objective Response ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Common Grade ◽  
Advanced Gastric Adenocarcinoma ◽  
Grade 3 ◽  
First Line Treatment

Objective.To evaluate the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the first line treatment of advanced gastric adenocarcinoma.Methods.A total of 37 patients were enrolled into this study, and they received DOX regimen (docetaxel 75 mg/m2and oxaliplatin 130 mg/m2intravenous infusion on day 1, and capecitabine 1000 mg/m2orally twice daily on d1–14); treatment was repeated every 3 weeks.Results.All 37 patients were assessable for evaluation. The numbers of patients with complete response (CR), partial responses (PR), stable disease (SD), and progressive disease (PD) were 1, 10, 23, and 3, respectively. The objective response rate (ORR) was 29.7%, with the disease control rate (DCR) of 91.9%. Median progression-free survival (mPFS) and overall survival (mOS) were 197 days and 364 days, respectively. The most common grade 3/4 toxicities were hematological toxicities. The most common grade 3/4 nonhematological toxicities were fatigue, nausea, vomiting, anorexia, diarrhea, and hand-foot syndrome.Conclusion.The DOX regimen demonstrated a promising efficacy as the first line regimen in treating advanced gastric cancer patients with good performance status, the toxicities were tolerated and controllable. Large-scale clinical observation is necessary to get further evidence.

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; &lt;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.

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