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Future Oncology (London, England) Jul 2021Monoclonal antibodies are highly complex, large and biologic products with a substantial impact on the clinical management of a variety of diseases including cancer.... (Comparative Study)
Comparative Study Review
Monoclonal antibodies are highly complex, large and biologic products with a substantial impact on the clinical management of a variety of diseases including cancer. The expiry of patents for essential monoclonal antibodies in cancer care such as bevacizumab, rituximab and trastuzumab, has prompted the global development of biosimilars to balance the biologics market. However, an understanding of the different approach of biosimilar development compared with its reference medicinal product, especially in the context of clinical trial design and end point selection may help oncologists integrating biosimilars into clinical practice. Herein, we reviewed the clinical development of biosimilars in oncology comparing the available clinical data of proposed biosimilars of bevacizumab, rituximab and trastuzumab.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Biosimilar Pharmaceuticals; Drug Development; Equivalence Trials as Topic; Humans; Medical Oncology; Neoplasms; Research Design; Rituximab; Trastuzumab
PubMed: 33904318
DOI: 10.2217/fon-2020-0923 -
Praxis Apr 2017
Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Disease-Free Survival; Glioblastoma; Humans; Neoplasm Recurrence, Local
PubMed: 28401779
DOI: 10.1024/1661-8157/a002650 -
BMC Cancer Jun 2023Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in... (Review)
Review
BACKGROUND
Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM).
METHODS
PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity).
RESULTS
Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear.
CONCLUSIONS
Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.
Topics: Humans; Glioblastoma; Bevacizumab; Quality of Life; Brain; Drug-Related Side Effects and Adverse Reactions
PubMed: 37316802
DOI: 10.1186/s12885-023-11043-6 -
European Review For Medical and... Nov 2021The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients.
MATERIALS AND METHODS
We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events.
RESULTS
A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively).
CONCLUSIONS
This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34787852
DOI: 10.26355/eurrev_202111_27092 -
Oncology Research and Treatment 2022The use of bevacizumab in patients with previously treated metastatic breast cancer (MBC) is controversial. This meta-analysis was carried out to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of bevacizumab in patients with previously treated metastatic breast cancer (MBC) is controversial. This meta-analysis was carried out to evaluate the efficacy and safety of the regimen including bevacizumab among patients with pretreated MBC.
METHODS
We systematically searched PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials evaluating bevacizumab combined with chemotherapy for previously treated MBC patients. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS) and toxicity. The risk of bias was assessed by the Cochrane Collaboration's tool. The pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were calculated for the identified studies. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
RESULTS
Four studies involving 1,640 individuals were included. Pooling results showed that the PFS of bevacizumab-containing groups (HR 0.82; 95% CI 0.73-0.93, p = 0.002) was significantly better than that of the control groups, especially when bevacizumab was administered as the second-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-negative MBC (HR 0.77; 95% CI 0.66-0.88, p = 0.0002). The ORR in the bevacizumab-containing group was superior to that in the control group, both in the general (RR 1.45; 95% CI 1.18-1.78, p = 0.0004) and HER2-negative groups (RR 1.30; 95% CI 1.03-1.63, p = 0.03). However, no significant effect on OS was demonstrated for the addition of bevacizumab to the second-line treatment for HER2-negative MBC (HR 0.93; 95% CI 0.79-1.10, p = 0.39). Comparatively, proteinuria was more common in the bevacizumab-containing group. In addition, the application of bevacizumab tended to result in therapy discontinuation due to treatment-related toxicity.
CONCLUSIONS
Bevacizumab-containing chemotherapy, in light of its favorable effects on clinical outcomes, could be a preferred therapeutic option for patients with MBC, for whom the disease must be rapidly relieved. Further studies are warranted for exploring the advantageous patients with the receipt of bevacizumab in multiline treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Disease-Free Survival; Female; Humans
PubMed: 35882206
DOI: 10.1159/000525882 -
Balkan Medical Journal Jan 2021Bevacizumab-combined chemotherapy is a new regimen for advanced/recurrent endometrial cancer. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bevacizumab-combined chemotherapy is a new regimen for advanced/recurrent endometrial cancer.
AIMS
To evaluate the efficacy and safety of bevacizumab-combined chemotherapy in advanced/recurrent endometrial cancer.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
Eligible studies were retrieved from Embase, PubMed, and Cochrane Library. The data of primary outcomes including progression-free survival and overall survival and secondary outcomes including overall survival, response rate, and adverse events (grade ≥2) were extracted, pooled, and used for the meta-analysis to compare the efficacy and safety of bevacizumab-combined chemotherapy with other treatments in patients with advanced/recurrent endometrial cancer.
RESULTS
Notably, 2 randomized-controlled and 5 single-arm trials of bevacizumab-combined chemotherapy or bevacizumab single-agent therapy for endometrial cancer were included. Meta-analysis indicated that bevacizumab-combined chemotherapy significantly increased the progression-free survival rate (hazard ratio=0.82, 95% confidence interval=0.70, 0.97) and overall survival rate (hazard ratio=0.83, 95% confidence interval=0.70, 0.98) compared with chemotherapy alone. The rates of overall, complete, and partial response to bevacizumab-combined chemotherapy were 76%, 22%, and 21%, respectively. The 6 and 12-month disease-free progression rates after bevacizumab-combined chemotherapy were 79% and 62%, respectively. Anemia (23%), leukopenia (46%), neutropenia (51%), hypertension (16%), and fatigue (24%) were the general adverse events after bevacizumab-combined chemotherapy.
CONCLUSION
Bevacizumab-combined chemotherapy may have a higher efficacy in improving the overall and progression-free survival in patients with advanced/recurrent endometrial cancers compared with chemotherapy alone.
Topics: Bevacizumab; Drug Combinations; Drug Therapy; Endometrial Neoplasms; Female; Humans; Randomized Controlled Trials as Topic
PubMed: 33593716
DOI: 10.5152/balkanmedj.2021.20121 -
Translational Vision Science &... Jul 2021To examine the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells (HCEpCs) and human corneal endothelial cells (HCEnCs),...
PURPOSE
To examine the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells (HCEpCs) and human corneal endothelial cells (HCEnCs), as well as human retinal pigment epithelial (ARPE-19) cells for comparison.
METHODS
Immortalized cell lines of HCEpCs, HCEnCs, and ARPE-19 cells were exposed to clinically relevant concentrations of bevacizumab (0.313-5.00 mg/mL). The ApoTox-Glo Triplex Assay was used to assess cell viability, cytotoxicity, and apoptosis, and the Mitochondrial ToxGlo Assay was used to assess cell membrane integrity and adenosine triphosphate (ATP) levels after a 24-hour treatment period.
RESULTS
Across all three cell types, we observed similar results of a decrease in cell viability at 5.00 mg/mL (P < 0.05) and an increase in cytotoxicity at 5.00 mg/mL (P < 0.05), whereas apoptotic activity remained unchanged (P > 0.05), which is a profile consistent with cells undergoing primary necrosis at high concentrations. Additionally, cell membrane integrity was compromised at 5.00 mg/mL (P < 0.05), whereas no decrease in ATP levels were observed (P > 0.05). Thus, no interference with mitochondrial oxidative phosphorylation in ATP production was seen, and the cells were able to maintain normal metabolic levels at high concentrations of bevacizumab.
CONCLUSIONS
HCEpCs, HCEnCs, and ARPE-19 cells experience a decrease in viability and undergo primary necrosis when exposed to bevacizumab at a concentration of 5.00 mg/mL; however, they are able to maintain normal metabolism and mitochondrial function at the high concentrations used for the treatment of corneal neovascularization.
TRANSLATIONAL RELEVANCE
This study provides safety data on the concentrations of bevacizumab injected intravitreally and complements clinical data showing toxicity of topical bevacizumab on corneal epithelial and endothelial cells.
Topics: Angiogenesis Inhibitors; Bevacizumab; Cell Survival; Endothelial Cells; Humans; Vascular Endothelial Growth Factor A
PubMed: 34323952
DOI: 10.1167/tvst.10.8.32 -
PloS One 2022Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic...
Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.
Topics: Adenoviridae; Animals; Apoptosis; Bevacizumab; Cell Line, Tumor; Chemokines; Genetic Therapy; Glioblastoma; Glioma; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplastic Processes
PubMed: 36006934
DOI: 10.1371/journal.pone.0273242 -
Current Oncology (Toronto, Ont.) Sep 2023Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation.... (Review)
Review
Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.
Topics: Humans; Female; Bevacizumab; Prospective Studies; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Peritoneal Neoplasms; Ovarian Neoplasms
PubMed: 37754507
DOI: 10.3390/curroncol30090592 -
Targeted Oncology Oct 2017Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab,... (Review)
Review
Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability. As a result, outcomes for patients with mCRC may be worsened. Additionally, counterfeit bevacizumab has infiltrated legitimate supply chains, exposing patients to risk. Oncologists may also be affected detrimentally, since resolving access issues can be time-consuming and demoralizing. The imminent expiry of patents protecting bevacizumab provides other manufacturers with the opportunity to produce highly similar versions known as biosimilars. High-quality, safe, and effective biosimilars have the potential to expand access to bevacizumab. Most of the bevacizumab biosimilars currently in development are in clinical trials in patients with non-small-cell lung cancer, and future authorization for mCRC indications will, therefore, be based on extrapolation. This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Biosimilar Pharmaceuticals; Colorectal Neoplasms; Humans
PubMed: 28801849
DOI: 10.1007/s11523-017-0518-1