A Novel Combination of Bevacizumab with Chemotherapy Improves Therapeutic Effects for Advanced Biliary Tract Cancer: A Retrospective, Observational Study.
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ABSTRACT: Background
Biliary tract cancer (BTC) is a heterogenous collection of biliary tract cancer at different primary sites, and the prognosis of advanced BTC is dismal. Systemic chemotherapy with gemcitabine and cisplatin (GC) has been the reference regimen since 2010. How to improve therapeutic effects of GC regimen is an urgent mission at present.Methods
Bevacizumab with a reduced dosage and modified schedule (10 mg/Kg/triweekly, 1 day before GS at the first 2 cycles) was combined with standard GC for patients with advanced BTC. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 every 2 months. Kaplan-Meier curves were estimated for time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS).Result
A total of thirty cases of advanced BTC accepted this treatment, and the overall response rate (ORR) was 50.0%, and the disease control rate was 80.0% for all patients. The median TTF was 5.8 months, the median PFS was 8.4 months, and the median OS was 13.6 months. Most responses were noted at the first evaluation. Adverse effects (AEs) were mostly tolerable.Conclusions
After modifying the schedule, adding bevacizumab to a traditional GC regimen could increase the ORR with a shorter time-to-response, a better PFS and OS than GC alone but without the addition of AE. This regimen can be applied to patients with advanced BTC, especially those who are with a big tumor burden and who need a rapid response.
SUBMITTER: Pei SN
PROVIDER: S-EPMC8345065 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAdvanced biliary tract cancer (BTC) has a poor prognosis. Gemcitabine with platinum chemotherapy was the standard first-line chemotherapeutic regimen until the recent addition of anti-PD-1/PD-L1 antibodies. After disease progression, the only second-line chemotherapy that has demonstrated a survival benefit versus supportive care is FOLFOX (folinic acid, fluorouracil, and oxaliplatin), with a modest benefit. This study aimed to assess the efficacy and safety of second-line FOLFIRI (folinic acid, fluorouracil, and irinotecan) combined with bevacizumab for advanced BTC.MethodsThis single-center retrospective study enrolled patients with metastatic BTC (intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder carcinoma) that progressed after first-line gemcitabine-based chemotherapy. FOLFIRI-bevacizumab was administered intravenously every 2 weeks [folinic acid 200 mg/m², fluorouracil 400 mg/m² (bolus), fluorouracil 2400 mg/m² (46-h continuous intravenous infusion), irinotecan 180 mg/m², and bevacizumab 5 mg/kg] until unacceptable toxicity, patient refusal, or disease progression.ResultsOverall, 28 patients received the FOLFIRI-bevacizumab regimen after gemcitabine-based chemotherapy. The median overall survival (OS) was 9.0 months (95% CI 6.4-16.5). The OS rate was 39.3% (95% CI 24.8-62.3) and 10.7% (95% CI 3.7-32.1) at 12- and 24-months respectively. The median progression-free survival (PFS) was 5.2 months (95% CI 3.1-10.2) with FOLFIRI-bevacizumab. The PFS rates at 12 months and 24 months were 17.9% (95% CI 8.19-39.5] and 10.7% (95% CI 3.7-31.2), respectively. The overall response rate (ORR) to FOLFIRI-bevacizumab was 23.1%, with a disease control rate (DCR) of 69.3%. Grade 3-4 adverse events (sAE) were reported in 20 patients (71.4%) treated with FOLFIRI-bevacizumab.ConclusionFOLFIRI-bevacizumab as a second-line treatment for advanced BTC after gemcitabine-based chemotherapy showed efficacy and safety with a promising tumor response rate in this retrospective single-center study.
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Project description:BackgroundBiliary tract cancers (BTCs) are heterogenous, highly aggressive tumors that harbor a dismal prognosis for which more effective treatments are needed. The role of cancer immunotherapy in BTC remains to be characterized. The tumor microenvironment (TME) of BTC is highly immunosuppressed and combination treatments are needed to promote effective anticancer immunity. Vascular endothelial growth factor (VEGF) drives immunosuppression in the TME by disrupting antigen presentation, limiting T-cell infiltration, or potentiating immune-suppressive cells. Many VEGF-regulated mechanisms are thought to be relevant to repressed antitumor immunity in BTC, making dual targeting of VEGF and programmed cell death protein 1 (PD-1)/PD-L1 pathways a rational approach. Gemcitabine and Cisplatin (Gem/Cis) can also modulate anticancer immunity through overlapping and complementary mechanisms to those regulated by VEGF. Anti-PD-L1/VEGF inhibition, coupled with chemotherapy, may potentiate antitumor immunity leading to enhanced clinical benefit.MethodsIMbrave 151 is a randomized, double-blind, placebo-controlled, multicenter, international phase II study to evaluate atezolizumab (a PD-L1 inhibitor) in combination with chemotherapy (gemcitabine and cisplatin) and bevacizumab (an anti-VEGF monoclonal antibody) as a first-line treatment for advanced BTC. Approximately 150 patients with previously untreated, advanced BTC will be randomized to either Arm A (atezolizumab + bevacizumab + Gem/Cis) or Arm B (atezolizumab + placebo + Gem/Cis). Randomization is stratified by the presence of metastatic disease, primary tumor location, and geographic region. The primary efficacy endpoint is investigator-assessed progression-free survival (PFS) per RECIST 1.1. Secondary endpoints include objective response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and safety and patient reported outcomes (PROs). Tissue, blood, and stool samples will be collected at baseline and on-treatment in order to perform correlative biomarker analyses.DiscussionIMbrave 151 represents the first randomized study to evaluate combined PD-L1/VEGF blockade on a chemotherapy backbone in BTC.Trial registrationNCT identifier: NCT04677504; EUDRACT number: 2020-003759-14.
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Project description:Background & aimsAdvanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors.MethodsFrom January 2010 until December 2019, 142 patients started palliative chemotherapy at our tertiary care liver center. Overall survival (OS) was calculated using Kaplan-Meier plots. Prognostic factors were evaluated using cox proportional-hazards.ResultsPatients received a median number of 2 lines of chemotherapy. Median OS was 6.7, 15.2 and 18.2 months for patients who received 1, 2 and 3 lines of chemotherapy, respectively. Patients treated with FOLFIRINOX had a significantly extended OS of 23.8 months (log-rank test: p = 0.018). The univariate cox regression analysis identified several clinical parameters associated with survival (e.g. albumin, bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 levels).ConclusionsOur study provides real-world data on the prognosis of ABTC including survival times for patients receiving third and later lines of chemotherapy.Lay summaryReal-world data depicting the outcome of patients with advanced biliary tract cancer outside the framework of controlled trials remain rare despite being extremely important for clinical decision-making. This study therefore provides important real-world data on the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX, as well as on other chemotherapy regimens or later lines of chemotherapy. It further demonstrates that the use of FOLFIRINOX is associated with promising survival and that there is an association between various clinical parameters such as pre-therapeutic albumin, bilirubin or carbohydrate antigen 19-9 levels and survival.
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Project description:BackgroundMalignant tumors of the biliary system are characterized by a high degree of malignancy and strong invasiveness, and they are usually diagnosed at late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are two of the options available to improve prognosis and delay tumor progression. This study aimed to comprehensively evaluate the safety and effectiveness of various chemotherapy schemes for the treatment of advanced biliary tract cancer in published systematic reviews and meta-analyses (SRoMAs).MethodsAn umbrella review method was adopted, which aims to summarize the existing evidence from multiple studies around a research topic. SRoMAs up to April 9, 2022, were identified using PubMed, Web of Science, the Cochrane database, and manual screening. Eligible studies were screened according to inclusion and exclusion criteria. This study had been registered at PROSPERO (CRD42022324548). For each eligible study, we extracted the data of general characteristics and the main findings. The methodological quality of the included studies were assessed by the AMSTAR2 scale, and the quality of evidence was evaluated by the GRADE tools.ResultsA total of 1833 articles were searched; 14 unique articles with 94 outcomes were identified by eligibility criteria. The incidence of skin rash (RR = 18.11, 95% CI 5.13-63.91, GRADE: Moderate) and diarrhea (RR = 2.48, 95% CI 1.2-5.10, GRADE: Moderate) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine monotherapy. The number of patients receiving gemcitabine-based chemotherapy who developed leukopenia (OR = 7.17, 95% CI 1.43-36.08, GRADE: Moderate), anemia (OR = 7.04, 95% CI 2.59-19.12, GRADE: High), thrombocytopenia (RR = 2.45, 95% CI 1.39-4.32, GRADE: Moderate), and neutropenia (RR = 3.30, 95% CI 1.04-10.50, GRADE: Moderate) was significantly higher than that of patients who received gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR = 2.46, 95% CI 1.27-4.57, GRADE: Moderate) than patients receiving S-1 + gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR = 0.83, 95% CI 0.7-0.99, GRADE: Moderate), higher DCR (0R = 5.18, 95% CI 3.3-10.23, GRADE: Moderate), and higher ORR (0R = 3.24, 95% CI 1.18-8.92, GRADE: Moderate) compared with patients who received 5-FU/LV monotherapy or supportive therapy. Surprisingly, we found evidence that gemcitabine-based chemotherapy did not improve postoperative patients' OS (HR = 0.91, 95% CI 0.74-1.12, GRADE: Moderate) when compared with best supportive care.ConclusionsThis study comprehensively evaluated the safety and efficacy of chemotherapy or targeted therapy regimens for advanced biliary tract cancer and found 11 outcomes with "Moderate" or "High" levels; however, most of the outcomes were still at "low" or "very low" levels. More randomized controlled studies are needed in the future to further summarize high levels of evidence.
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