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Critical Reviews in Oncology/hematology Jun 2024Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis.
METHODS
Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences were searched until February 29, 2024. The main outcomes of interest were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs).
RESULTS
We analyzed 16 RCTs with a total of 5018 patients. Among first-line therapies, nivolumab and ipilimumab significantly increased OS and resulted in fewer grade ≥3 TRAEs. Bevacizumab plus chemotherapy significantly increased PFS. Among salvage therapies, ramucirumab and chemotherapy was associated with the best OS and PFS, but resulted in more grade ≥3 TRAEs. Subgroup analysis by histologic types suggested that in first-line settings, bevacizumab and chemotherapy increase OS the most for epithelioid type, while the nivolumab plus ipilimumab treatment increases OS the most for non-epithelioid type. In salvage therapies, ramucirumab and chemotherapy increase OS for both epithelioid and non-epithelioid types.
CONCLUSION
Nivolumab plus ipilimumab was associated with the best OS among first-line treatments. Ramucirumab and chemotherapy was associated with the best clinical outcomes in salvage settings. Treatment for malignant mesothelioma should be tailored based on different clinicopathological characteristics.
Topics: Humans; Salvage Therapy; Mesothelioma, Malignant; Antineoplastic Combined Chemotherapy Protocols; Network Meta-Analysis; Randomized Controlled Trials as Topic; Ramucirumab
PubMed: 38677356
DOI: 10.1016/j.critrevonc.2024.104372 -
Critical Reviews in Oncology/hematology Jun 2024This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy... (Review)
Review
PURPOSE
This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment.
METHODS
A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature.
RESULTS
VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection.
CONCLUSION
While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
Topics: Humans; Glioblastoma; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Brain Neoplasms; Antineoplastic Agents
PubMed: 38677355
DOI: 10.1016/j.critrevonc.2024.104365 -
Survey of Ophthalmology 2024In recent years, the progress made in the field of optical coherence tomography has helped to understand the changes in eye layers in patients with exudative age-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, the progress made in the field of optical coherence tomography has helped to understand the changes in eye layers in patients with exudative age-related macular degeneration (nAMD). Early diagnosis of nAMD, a leading cause of irreversible vision impairment, is helpful. Therefore, we performed a meta-analysis on OCT measurement alterations before and after anti-VEGF therapy in patients with nAMD and controls.
METHOD
We systematically searched Scopus, PubMed, Cochrane, and Web of Science to find articles that measured choroidal and retinal layer changes after anti-VEGF therapy in nAMD Patients. We chose either a fixed-effects or random-effects model based on the assessed heterogeneity level to perform a meta-analysis. In addition, we conducted meta-regression, subgroup analyses, publication bias, and quality assessment for included studies.
RESULTS
Thirteen studies were included in the meta-analysis, with 733 total participants. Foveal thickness and subfoveal choroidal thickness (CT) decreased significantly in the first 3 years after injections, except for subfoveal CT in the third year after injection. It also showed that CT at 1500 µm temporal and nasal to the fovea did not significantly change.
CONCLUSION
Our results showed anti-VEGF treatment for nAMD patients was associated with a significant reduction in foveal thickness and subfoveal CT in the first 2 years after treatment. Our analysis did not reveal any correlation between changes in foveal thickness and subfoveal CT with best-corrected visual acuity or other factors.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Choroid; Intravitreal Injections; Ranibizumab; Retina; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 38641181
DOI: 10.1016/j.survophthal.2024.04.001 -
Drugs May 2024The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis.
METHODS
A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan-Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data.
RESULTS
A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data.
CONCLUSIONS
This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies.
Topics: Humans; Psoriasis; Interleukin-17; Interleukin-23; Antibodies, Monoclonal, Humanized; Dermatologic Agents
PubMed: 38630365
DOI: 10.1007/s40265-024-02028-1 -
Scandinavian Journal of Gastroenterology Jul 2024Thalidomide has been used for angioectasia-associated refractory gastrointestinal bleeding (GIB), with studies showing variable efficacy and side effects profile. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thalidomide has been used for angioectasia-associated refractory gastrointestinal bleeding (GIB), with studies showing variable efficacy and side effects profile. We conducted a meta-analysis to reconcile the data.
METHODS
Online databases were searched for studies evaluating thalidomide in patients with refractory/recurrent GIB due to angioectasias. The outcomes of interest were cessation of bleeding, rebleeding, need for blood transfusion, hospitalization and adverse events. Pooled proportions for incidence, and odds ratios (OR) for comparison with control were calculated along with 95% confidence interval (CI).
RESULTS
A total of seven studies with 346 patients ( = 269 thalidomide, = 77 control) were included. Thalidomide dose was usually started at 50-100mg/day. The mean age was 65 years, 45% patients were men, and mean follow-up was 1.8 years. The pooled clinical outcomes with thalidomide were: cessation of bleeding 42.2% (95% CI 36.02 to 48.41), rebleeding 30%, need for blood transfusion 20.1%, hospitalization 40% and adverse events 55.9%. When compared with the control group in 2 studies, patients on thalidomide had significantly higher odds of cessation of bleeding (OR 21.40, 95% CI 5.78 to 79.29, < 0.00001) and adverse events, with lower need for blood transfusion and hospitalization.
DISCUSSION
In patients with angioectasias-related refractory/recurrent GIB, the use of thalidomide results in significantly decreased bleeding risk and may play a role in the management of such patients.
Topics: Female; Humans; Angiogenesis Inhibitors; Blood Transfusion; Gastrointestinal Hemorrhage; Hospitalization; Recurrence; Thalidomide; Treatment Outcome
PubMed: 38629130
DOI: 10.1080/00365521.2024.2342404 -
European Archives of... Apr 2024To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally... (Review)
Review
PURPOSE
To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma.
METHODS
The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies).
RESULTS
A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05-1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12-1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16-11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04-3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05).
CONCLUSION
Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2023-8-0076/ , registration number INPLASY202380076.
PubMed: 38625559
DOI: 10.1007/s00405-024-08545-9 -
Journal of Neuro-oncology May 2024Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms.
METHODS
PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes.
RESULTS
Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT).
CONCLUSION
Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.
Topics: Humans; Bevacizumab; Radiation Injuries; Necrosis; Laser Therapy; Central Nervous System Neoplasms; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors
PubMed: 38619777
DOI: 10.1007/s11060-024-04650-1 -
Advances in Therapy Jun 2024Gastric cancer has the highest incidence and mortality in Eastern Asia. The efficacy and safety of ramucirumab (RAM) monotherapy or in combination with paclitaxel (PTX)... (Review)
Review
Real-World Effectiveness and Safety of Ramucirumab as a Second-Line Treatment for Patients with Unresectable Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma in Japan and South Korea: A Systematic Literature Review.
INTRODUCTION
Gastric cancer has the highest incidence and mortality in Eastern Asia. The efficacy and safety of ramucirumab (RAM) monotherapy or in combination with paclitaxel (PTX) for patients with unresectable advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (G/GEA) have been established in clinical trials. To assess the effectiveness and safety of RAM or RAM-based therapy as a second-line treatment in real-world clinical practice in Eastern Asia and to pave the way for future research, a systematic literature review (SLR) was conducted.
METHODS
Studies published between January 2014 and December 2021 were identified in PubMed, Embase, Cochrane Library, CNKI, Wanfang, and CBM databases.
RESULTS
This SLR included 23 studies from Japan and South Korea, of which 22 were retrospective and 11 were full-text articles. Most studies investigated RAM + PTX (range of median overall survival [mOS] 7.4-12.2 months; median progression-free survival [mPFS] 3.35-7.0 months). Data were limited for RAM, RAM + albumin-bound paclitaxel, and RAM + taxane. RAM + PTX was associated with longer survival (mOS 9.3-12.2 months vs. 5.2-9.7 months; mPFS 4.1-5.1 months vs. 3.0-4.1 months) than PTX. Patients with prior anti-programmed cell death 1 (anti-PD-1) exposure experienced longer mPFS (4.8 vs. 3.4 months) from RAM + taxane than those without prior anti-PD-1 exposure. Few patients (3.3-6.3%) discontinued RAM or RAM-based therapy because of adverse events (AEs). Hematological toxicities were most frequently occurring AEs and no new safety signals were identified compared to clinical trials.
CONCLUSION
RAM + PTX as a second-line treatment is effective and associated with an acceptable toxicity profile in patients with advanced or metastatic G/GEA in real-world settings of Japan and South Korea. More studies are recommended to further evaluate effectiveness and safety of RAM or RAM-based therapy, especially after anti-PD-1 therapy, in a wider Eastern Asian population.
TRIAL REGISTRATION
INPLASY registration number INPLASY2022120023.
Topics: Ramucirumab; Humans; Stomach Neoplasms; Antibodies, Monoclonal, Humanized; Adenocarcinoma; Esophagogastric Junction; Republic of Korea; Esophageal Neoplasms; Paclitaxel; Japan; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 38619719
DOI: 10.1007/s12325-024-02838-5 -
American Journal of Hematology Jul 2024In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.
In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.
Topics: Multiple Myeloma; Humans; Lenalidomide; Dexamethasone; Oligopeptides; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival; Treatment Outcome
PubMed: 38606993
DOI: 10.1002/ajh.27314 -
Expert Opinion on Drug Discovery May 2024ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into... (Review)
Review
INTRODUCTION
ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. However, the stability of these mediators must be improved, and they may require formulation to achieve optimal tissue concentrations.
AREAS COVERED
Herein, the author reviews the literature around chemical stabilization and formulation of ω-3 PUFA mediators and their application in anticancer drug discovery.
EXPERT OPINION
Aryl-urea bioisosteres of ω-3 PUFA epoxides that killed cancer cells targeted the mitochondrion by a novel dual mechanism: as protonophoric uncouplers and as inhibitors of electron transport complex III that activated ER-stress and disrupted mitochondrial integrity. In contrast, aryl-ureas that contain electron-donating substituents prevented cancer cell migration. Thus, aryl-ureas represent a novel class of agents with tunable anticancer properties. Stabilized analogues of other ω-3 PUFA-derived mediators could also be adapted into anticancer strategies. Indeed, a cocktail of agents that simultaneously promote cell killing, inhibit metastasis and angiogenesis, and that attenuate the pro-inflammatory microenvironment is a novel future anticancer strategy. Such regimen may enhance anticancer drug efficacy, minimize the development of anticancer drug resistance and enhance outcomes.
Topics: Animals; Humans; Antineoplastic Agents; Drug Discovery; Fatty Acids, Omega-3; Mitochondria; Neoplasms
PubMed: 38595031
DOI: 10.1080/17460441.2024.2340493