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Biomolecules Jun 2023Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the... (Review)
Review
BACKGROUND
Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the exact pathogenesis of this disease is unclear.
METHODS
In March 2022, Medline (Ovid), Embase (Ovid), Scopus, and Web of Science were screened to identify eligible in vitro studies investigating the effects of antiresorptive and antiangiogenic compounds on orally derived cells.
RESULTS
Fifty-nine articles met the inclusion criteria. Bisphosphonates were used in 57 studies, denosumab in two, and sunitinib and bevacizumab in one. Zoledronate was the most commonly used nitrogen-containing bisphosphonate. The only non-nitrogen-containing bisphosphonate studied was clodronate. The most frequently tested tissues were gingival fibroblasts, oral keratinocytes, and alveolar osteoblasts. These drugs caused a decrease in cell proliferation, viability, and migration.
CONCLUSIONS
Antiresorptive and antiangiogenic drugs displayed cytotoxic effects in a dose and time-dependent manner. Additional research is required to further elucidate the pathways of MRONJ.
Topics: Humans; Bone Density Conservation Agents; Bisphosphonate-Associated Osteonecrosis of the Jaw; Denosumab; Diphosphonates; Zoledronic Acid; Angiogenesis Inhibitors
PubMed: 37371553
DOI: 10.3390/biom13060973 -
European Review For Medical and... Nov 2022Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of triplet regimens based on pomalidomide and dexamethasone for treatment of relapsed/refractory multiple myeloma: a systematic review and meta-analysis.
OBJECTIVE
Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen.
MATERIALS AND METHODS
A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used.
RESULTS
Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%).
CONCLUSIONS
Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.
Topics: Humans; Multiple Myeloma; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Thalidomide
PubMed: 36394758
DOI: 10.26355/eurrev_202211_30162 -
European Journal of Gastroenterology &... Oct 2022We evaluated the efficacy of pharmacologic treatments for patients with overt or occult bleeding due to gastrointestinal angiodysplasias (GIADs). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We evaluated the efficacy of pharmacologic treatments for patients with overt or occult bleeding due to gastrointestinal angiodysplasias (GIADs).
METHODS
A systematic computer-aided literature search across Medline, Cochrane, Scopus and Embase databases was performed. Studies evaluating pharmacologic treatments for patients presenting with GIADs-related overt or occult bleeding were included. Post-treatment rebleeding was the primary outcome. Need for red blood cells (RBC) transfusion, post-treatment hemoglobin levels and adverse events rate comprised secondary outcomes. Results are presented as odds ratio (OR), mean difference (MD) or pooled rates (%) with 95% confidence intervals (95%CI).
RESULTS
Four types of pharmacologic treatment were identified (25 studies): somatostatin analogs, hormonal therapy, thalidomide and angiogenesis inhibitors. Pharmacologic treatment of any kind led to significantly reduced bleeding episodes [OR (95% CI), 0.08 (0.04-0.18)]. No pharmacologic treatment was superior to others ( P = 0.46). Overall, pooled rebleeding rate post-treatment was 34% (26-43%). Similarly, significantly fewer patients required RBC transfusion during the post-treatment period [0.03 (0.03-0.07)], with no differences among various treatments ( P = 0.83), yielding an overall pooled transfusion rate of 33% (19-46%). Administration of pharmacological treatment led to significant improvement in terms of hemoglobin levels [MD (95% CI), 3.21 g/dL (2.42-3.99)]. The pooled rate of adverse events was 32% (22-42%).
CONCLUSION
In patients with GIADs administration of any pharmacologic treatment significantly decreases rebleeding episodes and transfusions leading to higher hemoglobin values. One-third of them experience at least one adverse event related to the treatment.
Topics: Angiodysplasia; Blood Transfusion; Erythrocyte Transfusion; Gastrointestinal Hemorrhage; Hemoglobins; Humans
PubMed: 35913758
DOI: 10.1097/MEG.0000000000002414 -
Critical Reviews in Oncology/hematology Dec 2023The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC).... (Review)
Review
The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC). Their efficacy post-surgical resection remains a contentious point. Various phase 3 RCTs have assessed their potency. Amongst evaluated agents, sunitinib and pembrolizumab have demonstrated notable disease-free survival benefits. Sunitinib's potential is diminished due to absence of clear overall survival (OS) benefits and side-effect profile. Pembrolizumab shows better tolerance, conclusive OS data are forthcoming. This scenario underscores the pressing need for advanced risk stratification methods and discovery of novel biomarkers. Existing strategies, largely pre-dating TKI and ICI therapeutic era, lack sufficient accuracy in predicting relapse-risk. Our review offers a comprehensive analysis of key phase 3 RCTs, focusing on TKIs, mTOR-inhibitors, and ICIs for adjuvant RCC treatment. The intent is to shed light on the intricate landscape of RCC treatment, guiding future research directions for optimizing patient outcomes.
Topics: Humans; Carcinoma, Renal Cell; Sunitinib; Kidney Neoplasms; Neoplasm Recurrence, Local; Disease-Free Survival
PubMed: 37748694
DOI: 10.1016/j.critrevonc.2023.104144 -
ESMO Open Jun 2022The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study.
METHODS
A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2).
RESULTS
Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03).
CONCLUSION
In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Smoking
PubMed: 35696746
DOI: 10.1016/j.esmoop.2022.100507 -
Current Oncology (Toronto, Ont.) May 2023Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have expanded these options for subsets with specific molecular alterations, such as microsatellite instability (MSI)-high cancers, but additional treatments and combinations are in urgent need to improve outcomes and improve survival of this incurable disease. The fluoropyrimidine-derivative trifluridine, in combination with tipiracil, has been introduced as a third-line treatment, and more recently, it was studied in combination with bevacizumab. This meta-analysis reports on studies with this combination in clinical practice outside clinical trials.
METHODS
A literature search in the Medline/PubMed and Embase databases was executed for finding series of trifluridine/tipiracil with bevacizumab in metastatic colorectal cancer. Criteria for inclusion in the meta-analysis were English or French language of the report, inclusion of twenty or more patients with metastatic colorectal cancer treated with trifluridine/tipiracil in combination with bevacizumab outside of a trial and containing information regarding response rates, progression-free survival (PFS), and overall survival (OS). Information on the demographics of the patients and on adverse effects of treatment was also collected.
RESULTS
Eight series with a total of 437 patients were eligible for the meta-analysis. The performed meta-analysis discovered a summary response rate (RR) of 2.71% (95% confidence interval (CI): 1.11-4.32%) and a disease control rate (DCR) of 59.63% (95% CI: 52.06-67.21%). Summary PFS was 4.56 months (95% CI: 3.57-5.55 months), and summary OS was 11.17 months (95% CI: 10.15-12.19 months). Common adverse effects identified mirrored the adverse-effect profile of the two components of the combination.
CONCLUSION
The current systematic review and meta-analysis reports the efficacy of trifluridine/tipiracil with bevacizumab in advanced lines of therapy for metastatic colorectal cancer in the setting of clinical practice outside clinical trials. Discovery of predictive biomarkers of response to trifluridine/tipiracil with bevacizumab will promote the tailoring of this treatment to individual patients to maximize clinical benefit.
Topics: Humans; Bevacizumab; Uracil; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms
PubMed: 37366880
DOI: 10.3390/curroncol30060397 -
The Cochrane Database of Systematic... Jun 2023Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line).
OBJECTIVES
The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months).
SEARCH METHODS
We searched various electronic databases on 8 July 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence.
MAIN RESULTS
We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs.
AUTHORS' CONCLUSIONS
There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants.
Topics: Humans; Ranibizumab; Bevacizumab; Macular Edema; Diabetic Retinopathy; Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Network Meta-Analysis; Laser Coagulation; Diabetes Mellitus
PubMed: 38275741
DOI: 10.1002/14651858.CD007419.pub7 -
The Cochrane Database of Systematic... Apr 2023Many women, and other females, with epithelial ovarian cancer (EOC) develop resistance to conventional chemotherapy drugs. Drugs that inhibit angiogenesis (development... (Review)
Review
BACKGROUND
Many women, and other females, with epithelial ovarian cancer (EOC) develop resistance to conventional chemotherapy drugs. Drugs that inhibit angiogenesis (development of new blood vessels), essential for tumour growth, control cancer growth by denying blood supply to tumour nodules.
OBJECTIVES
To compare the effectiveness and toxicities of angiogenesis inhibitors for treatment of epithelial ovarian cancer (EOC).
SEARCH METHODS
We identified randomised controlled trials (RCTs) by searching CENTRAL, MEDLINE and Embase (from 1990 to 30 September 2022). We searched clinical trials registers and contacted investigators of completed and ongoing trials for further information.
SELECTION CRITERIA
RCTs comparing angiogenesis inhibitors with standard chemotherapy, other types of anti-cancer treatment, other angiogenesis inhibitors with or without other treatments, or placebo/no treatment in a maintenance setting, in women with EOC. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our outcomes were overall survival (OS), progression-free survival (PFS), quality of life (QoL), adverse events (grade 3 and above) and hypertension (grade 2 and above).
MAIN RESULTS
We identified 50 studies (14,836 participants) for inclusion (including five studies from the previous version of this review): 13 solely in females with newly-diagnosed EOC and 37 in females with recurrent EOC (nine studies in platinum-sensitive EOC; 19 in platinum-resistant EOC; nine with studies with mixed or unclear platinum sensitivity). The main results are presented below. Newly-diagnosed EOC Bevacizumab, a monoclonal antibody that binds vascular endothelial growth factor (VEGF), given with chemotherapy and continued as maintenance, likely results in little to no difference in OS compared to chemotherapy alone (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.88 to 1.07; 2 studies, 2776 participants; moderate-certainty evidence). Evidence is very uncertain for PFS (HR 0.82, 95% CI 0.64 to 1.05; 2 studies, 2746 participants; very low-certainty evidence), although the combination results in a slight reduction in global QoL (mean difference (MD) -6.4, 95% CI -8.86 to -3.94; 1 study, 890 participants; high-certainty evidence). The combination likely increases any adverse event (grade ≥ 3) (risk ratio (RR) 1.16, 95% CI 1.07 to 1.26; 1 study, 1485 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 2) (RR 4.27, 95% CI 3.25 to 5.60; 2 studies, 2707 participants; low-certainty evidence). Tyrosine kinase inhibitors (TKIs) to block VEGF receptors (VEGF-R), given with chemotherapy and continued as maintenance, likely result in little to no difference in OS (HR 0.99, 95% CI 0.84 to 1.17; 2 studies, 1451 participants; moderate-certainty evidence) and likely increase PFS slightly (HR 0.88, 95% CI 0.77 to 1.00; 2 studies, 2466 participants; moderate-certainty evidence). The combination likely reduces QoL slightly (MD -1.86, 95% CI -3.46 to -0.26; 1 study, 1340 participants; moderate-certainty evidence), but it increases any adverse event (grade ≥ 3) slightly (RR 1.31, 95% CI 1.11 to 1.55; 1 study, 188 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 3) (RR 6.49, 95% CI 2.02 to 20.87; 1 study, 1352 participants; low-certainty evidence). Recurrent EOC (platinum-sensitive) Moderate-certainty evidence from three studies (with 1564 participants) indicates that bevacizumab with chemotherapy, and continued as maintenance, likely results in little to no difference in OS (HR 0.90, 95% CI 0.79 to 1.02), but likely improves PFS (HR 0.56, 95% CI 0.50 to 0.63) compared to chemotherapy alone. The combination may result in little to no difference in QoL (MD 0.8, 95% CI -2.11 to 3.71; 1 study, 486 participants; low-certainty evidence), but it increases the rate of any adverse event (grade ≥ 3) slightly (RR 1.11, 1.07 to 1.16; 3 studies, 1538 participants; high-certainty evidence). Hypertension (grade ≥ 3) was more common in arms with bevacizumab (RR 5.82, 95% CI 3.84 to 8.83; 3 studies, 1538 participants). TKIs with chemotherapy may result in little to no difference in OS (HR 0.86, 95% CI 0.67 to 1.11; 1 study, 282 participants; low-certainty evidence), likely increase PFS (HR 0.56, 95% CI 0.44 to 0.72; 1 study, 282 participants; moderate-certainty evidence), and may have little to no effect on QoL (MD 6.1, 95% CI -0.96 to 13.16; 1 study, 146 participants; low-certainty evidence). Hypertension (grade ≥ 3) was more common with TKIs (RR 3.32, 95% CI 1.21 to 9.10). Recurrent EOC (platinum-resistant) Bevacizumab with chemotherapy and continued as maintenance increases OS (HR 0.73, 95% CI 0.61 to 0.88; 5 studies, 778 participants; high-certainty evidence) and likely results in a large increase in PFS (HR 0.49, 95% CI 0.42 to 0.58; 5 studies, 778 participants; moderate-certainty evidence). The combination may result in a large increase in hypertension (grade ≥ 2) (RR 3.11, 95% CI 1.83 to 5.27; 2 studies, 436 participants; low-certainty evidence). The rate of bowel fistula/perforation (grade ≥ 2) may be slightly higher with bevacizumab (RR 6.89, 95% CI 0.86 to 55.09; 2 studies, 436 participants). Evidence from eight studies suggest TKIs with chemotherapy likely result in little to no difference in OS (HR 0.85, 95% CI 0.68 to 1.08; 940 participants; moderate-certainty evidence), with low-certainty evidence that it may increase PFS (HR 0.70, 95% CI 0.55 to 0.89; 940 participants), and may result in little to no meaningful difference in QoL (MD ranged from -0.19 at 6 weeks to -3.40 at 4 months). The combination increases any adverse event (grade ≥ 3) slightly (RR 1.23, 95% CI 1.02 to 1.49; 3 studies, 402 participants; high-certainty evidence). The effect on bowel fistula/perforation rates is uncertain (RR 2.74, 95% CI 0.77 to 9.75; 5 studies, 557 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Bevacizumab likely improves both OS and PFS in platinum-resistant relapsed EOC. In platinum-sensitive relapsed disease, bevacizumab and TKIs probably improve PFS, but may or may not improve OS. The results for TKIs in platinum-resistant relapsed EOC are similar. The effects on OS or PFS in newly-diagnosed EOC are less certain, with a decrease in QoL and increase in adverse events. Overall adverse events and QoL data were more variably reported than were PFS data. There appears to be a role for anti-angiogenesis treatment, but given the additional treatment burden and economic costs of maintenance treatments, benefits and risks of anti-angiogenesis treatments should be carefully considered.
Topics: Humans; Female; Angiogenesis Inhibitors; Bevacizumab; Carcinoma, Ovarian Epithelial; Vascular Endothelial Growth Factor A; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 37185961
DOI: 10.1002/14651858.CD007930.pub3 -
Medicine Aug 2023Ranibizumab addition may benefit to improve the efficacy in patients with diabetic retinopathy than only photocoagulation, and this meta-analysis aims to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ranibizumab addition may benefit to improve the efficacy in patients with diabetic retinopathy than only photocoagulation, and this meta-analysis aims to explore the impact of ranibizumab addition on efficacy for diabetic retinopathy.
METHODS
PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of ranibizumab addition on patients with diabetic retinopathy for this meta-analysis.
RESULTS
Six randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for diabetic retinopathy, ranibizumab addition showed significantly increased number of neovascularization area reduction (OR = 4.20; 95% CI = 1.47-12.02; P = .007) and reduced fluorescein leakage (MD = -2.53; 95% CI = -3.31 to -1.75; P < .00001), but showed no obvious impact on neovascularization area (MD = -1.80; 95% CI = -3.68 to 0.08; P = .06), photocoagulation retreatment (OR = 1.03; 95% CI = 0.47-2.27; P = .94) or adverse events (OR = 1.45; 95% CI = 0.49-4.29; P = .50).
CONCLUSIONS
Ranibizumab combined with photocoagulation is effective to improve efficacy for diabetic retinopathy.
Topics: Humans; Ranibizumab; Diabetic Retinopathy; Angiogenesis Inhibitors; Bevacizumab; Vascular Endothelial Growth Factor A; Laser Coagulation; Intravitreal Injections; Diabetes Mellitus
PubMed: 37543834
DOI: 10.1097/MD.0000000000034170 -
Scientific Reports Jan 2024We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Bispecific; Intravitreal Injections; Macular Degeneration
PubMed: 38291069
DOI: 10.1038/s41598-024-52942-3