-
Therapeutic Advances in Medical Oncology 2024Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung...
BACKGROUND
Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) alterations have brought questions.
OBJECTIVES
To evaluate the efficacy and safety of these two treatment regimens in advanced NSCLC patients harboring EGFR mutations.
DESIGN
This study is a systematic review and meta-analysis.
DATA SOURCES AND METHODS
PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were extensively searched for relevant randomized controlled trials (RCTs) on 14 May 2023. Two researchers independently screened the literature, assessed quality, and extracted data. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The secondary outcomes were adverse events (AEs) and PFS stratified by patients' characteristics. STATA 17.0 software (StataCorp LLC, USA) was adopted for meta-analysis.
RESULTS
A total of four RCTs involving 390 patients were included. Overall, the risk of bias across the studies was moderate to low. Pooled results showed that compared to osimertinib alone, the addition of bevacizumab to osimertinib failed to show prolongation of PFS [hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.78-1.27], OS (HR = 1.01, 95% CI: 0.73-1.41), or improvement of the ORR (risk ratio = 1.12, 95% CI: 0.90-1.38), while an increased incidence of some AEs was observed, such as nausea, oral mucositis, hypertension, and proteinuria. Notably, combination treatment did significantly prolong the PFS in the subset of smokers (HR = 0.64, 95% CI: 0.44-0.94). A mild trend toward PFS benefit under the combined regimen was also noted in patients with brain metastases and first-line treatment, though not reaching statistical significance.
CONCLUSION
Based on the available evidence, the addition of bevacizumab to osimertinib could not provide additional survival benefits with higher but manageable toxicity for EGFR-mutant NSCLC patients. Osimertinib monotherapy remains the prioritized treatment. Further investigation is warranted.
PubMed: 38304850
DOI: 10.1177/17588359241227677 -
Renal Failure Dec 2023This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis...
PURPOSE
This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS).
METHODS
A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled.
RESULTS
18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE ( = 1) or LDL-A ( = 2). 2 of 3 HD patients ultimately discontinued dialysis.
CONCLUSION
EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.
Topics: Humans; Adult; Glomerulosclerosis, Focal Segmental; Proteinuria; Treatment Outcome; Kidney Transplantation; Kidney; Recurrence
PubMed: 36762994
DOI: 10.1080/0886022X.2023.2176694 -
Pediatric Nephrology (Berlin, Germany) Mar 2024Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors.
OBJECTIVES
This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer.
STUDY ELIGIBILITY CRITERIA
Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed.
RESULTS
Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m was 29% (95% CI 0.0-58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22-51%). Substantial heterogeneity was present, with I statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity.
LIMITATIONS
A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability.
CONCLUSIONS
Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.
Topics: Child; Humans; Antineoplastic Agents; Cisplatin; Glomerular Filtration Rate; Magnesium; Neoplasms; Renal Insufficiency
PubMed: 37726572
DOI: 10.1007/s00467-023-06149-9 -
Combinatorial Chemistry & High... 2024Anti-angiogenic agents could enhance tumor immunity response, and anti- angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anti-angiogenic agents could enhance tumor immunity response, and anti- angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell lung cancer (NSCLC). The efficacy of this combination therapy remains controversial and obscure.
AIM
We conducted a meta-analysis to evaluate the clinical efficacy and safety of this therapeutic strategy in patients with advanced NSCLC and provide more guidance for treating NSCLC clinically.
METHODS
A systematic literature search was performed in PubMed, Embase, Web of Science, CNKI, and Wanfang databases to identify relevant studies published up to December 2021. The primary endpoint was the objective response rate (ORR). Second endpoints were progression-free survival (PFS), overall survival (OS), and grade ≥3 AEs adverse events (AEs). The sensitivity analysis was conducted to confirm the stability of the results. STATA 15.0 was utilized for all pooled analyses.
RESULTS
Eleven studies were eventually included in the meta-analysis, involving 533 patients with advanced NSCLC. The pooled ORR rate was 27% (95% CI 18% to 35%; I =84.2%; p<0.001), while the pooled median PFS and OS was 5.84 months (95% CI 4.66 to 7.03 months; I=78.4%; p<0.001) and 14.20 months (95% CI 11.08 to 17.32 months; I=82.2%; p=0.001), respectively. Most common grade ≥3 AEs included hypertension, hand-foot syndrome, diarrhea, adrenal insufficiency, hyponatremia, proteinuria, rash, thrombocytopenia, and fatigue.
CONCLUSION
Anti-angiogenesis combined with immunotherapy demonstrated satisfactory antitumor activity and an acceptable toxicity profile in patients with advanced NSCLC. The pooled results of our meta-analysis provided further evidence supporting the favorable efficacy and safety of this therapeutic strategy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Angiogenesis Inhibitors; Immunotherapy
PubMed: 37559541
DOI: 10.2174/1386207326666230808112656 -
Systematic Reviews Feb 2024Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing chronic organ damage is still unclear. This systematic review and meta-analysis aimed to evaluate the role of hydroxyurea in preventing organ morbidity.
METHOD
We included original articles published in English from 1st January 1990 to 31st January 2023, reporting hydroxyurea therapy and organ damage from PubMed, Google Scholar, Scopus, and CrossRef databases. A total of 45 studies with 4681 sickle cell disease patients were evaluated for organ damage.
RESULTS
Our analysis showed that hydroxyurea intervention significantly lowered transcranial Doppler and tricuspid regurgitant velocity, with a standardized mean difference of - 1.03 (- 1.49; - 0.58); I = 96% and - 1.37 (CI - 2.31, - 0.42); I = 94%, respectively. Moreover, the pooled estimate for albuminuria showed a beneficial effect post-hydroxyurea therapy by reducing the risk of albuminuria by 58% (risk ratio of 0.42 (0.28; 0.63); I = 28%).
CONCLUSION
Our study found that a hydroxyurea dose above 20 mg/kg/day with a mean rise in HbF by 18.46% post-hydroxyurea therapy had a beneficial role in reducing transcranial doppler velocity, tricuspid regurgitant velocity, albuminuria, and splenic abnormality.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023401187.
Topics: Humans; Hydroxyurea; Antisickling Agents; Albuminuria; Anemia, Sickle Cell; Blood Transfusion
PubMed: 38331925
DOI: 10.1186/s13643-024-02461-z -
Cureus May 2024Chronic kidney disease (CKD) is a progressive condition characterized by gradual loss of kidney function, necessitating timely monitoring and interventions. This... (Review)
Review
Chronic kidney disease (CKD) is a progressive condition characterized by gradual loss of kidney function, necessitating timely monitoring and interventions. This systematic review comprehensively evaluates the application of artificial intelligence (AI) and machine learning (ML) techniques for predicting CKD progression. A rigorous literature search identified 13 relevant studies employing diverse AI/ML algorithms, including logistic regression, support vector machines, random forests, neural networks, and deep learning approaches. These studies primarily aimed to predict CKD progression to end-stage renal disease (ESRD) or the need for renal replacement therapy, with some focusing on diabetic kidney disease progression, proteinuria, or estimated glomerular filtration rate (GFR) decline. The findings highlight the promising predictive performance of AI/ML models, with several achieving high accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve scores. Key factors contributing to enhanced prediction included incorporating longitudinal data, baseline characteristics, and specific biomarkers such as estimated GFR, proteinuria, serum albumin, and hemoglobin levels. Integration of these predictive models with electronic health records and clinical decision support systems offers opportunities for timely risk identification, early interventions, and personalized management strategies. While challenges related to data quality, bias, and ethical considerations exist, the reviewed studies underscore the potential of AI/ML techniques to facilitate early detection, risk stratification, and targeted interventions for CKD patients. Ongoing research, external validation, and careful implementation are crucial to leveraging these advanced analytical approaches in clinical practice, ultimately improving outcomes and reducing the burden of CKD.
PubMed: 38864072
DOI: 10.7759/cureus.60145 -
The Cochrane Database of Systematic... Jun 2024Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence suggests that metformin targets a number of pathways that lead to chronic kidney damage, and long-term use may, therefore, slow the rate of kidney function decline and chronic kidney disease (CKD) progression.
OBJECTIVES
To evaluate the effect of metformin therapy on kidney function decline in patients with CKD with or without diabetes mellitus and assess the safety and dose tolerability in this population.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2023 with assistance from an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that reported kidney-related outcomes with a minimum duration of 12 months delivery of the metformin intervention and whose eligibility criteria included adult participants with either i) a diagnosis of CKD of any aetiology and/or ii) those with a diagnosis of diabetes mellitus. Comparisons included placebo, no intervention, non-pharmacological interventions, other antidiabetic medications or any other active control. Studies that included patients on any modality of kidney replacement therapy were excluded.
DATA COLLECTION AND ANALYSIS
Two authors independently carried out data extraction using a standard data extraction form. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
This review included 11 studies reporting on 8449 randomised participants. Studies were conducted in patient populations with Autosomal Dominant Polycystic Kidney Disease (ADPKD) (four studies) or diabetes mellitus (seven studies). Six studies compared metformin with no active control, four studies compared metformin with active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), and one study included treatment arms that randomised to either metformin, diet and lifestyle modifications, or other antidiabetic therapies. The risk of bias in included studies varied; two studies were abstract-only publications and were judged to have a high risk of bias in most domains. Other included publications were judged to have a low risk of bias in most domains. Across comparisons, GRADE evaluations for most outcomes were judged as low or very low certainty, except for those relating to side effects, tolerance, and withdrawals, which were judged as moderate certainty. The evidence suggests that compared to placebo, metformin may result in i) a slightly smaller decline in kidney function (3 studies, 505 participants: MD 1.92 mL/min, 95% CI 0.33 to 3.51; I = 0%; low certainty), ii) very uncertain effects on the incidence of kidney failure (1 study, 753 participants: RR 1.20, 95% CI 0.17 to 8.49), iii) little or no effect on death (3 studies, 865 participants: RR 1.00, 95% CI 0.76 to 1.32; I = 0%; moderate certainty), iv) little or no effect on the incidence of serious adverse events (3 studies, 576 participants: RR 1.15, 95% CI 0.76 to 1.72; I = 0%; moderate certainty), and v) likely higher incidence of intolerance leading to study withdrawal than placebo (4 studies, 646 participants: RR 2.19, 95% CI 1.46 to 3.27; I = 0%; moderate certainty). The certainty of the evidence for proteinuria was very uncertain. Compared to other active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), metformin i) demonstrated very uncertain effects on kidney function decline, ii) may result in little or no difference in death (3 studies, 5608 participants: RR 0.95 95% CI 0.63 to 1.43; I = 0%; low certainty), iii) probably results in little or no difference in intolerance leading to study withdrawal (3 studies, 5593 participants: RR 0.92, 95% CI, 0.79 to 1.08; I = 0%; moderate certainty), iv) probably results in little or no difference in the incidence of serious adverse events (2 studies, 5545 participants: RR 1.16, 95% CI 0.79 to 1.71; I = 0%; moderate certainty), and v) may increase the urinary albumin-creatinine ratio (2 studies, 3836 participants: MD 14.61, 95% CI 8.17 to 21.05; I = 0%; low certainty). No studies reported the incidence of kidney failure.
AUTHORS' CONCLUSIONS
This review highlights the lack of RCTs reporting on the effects of metformin on kidney function, particularly in patients with CKD. Future research in this field requires adequately powered RCTs comparing metformin to placebo or standard care in those with CKD. Seven ongoing studies were identified in this review, and future updates, including their findings, may further inform the results of this review.
Topics: Metformin; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Disease Progression; Hypoglycemic Agents; Glomerular Filtration Rate; Diabetes Mellitus, Type 2; Adult; Bias
PubMed: 38837240
DOI: 10.1002/14651858.CD013414.pub2 -
Medicine Jan 2024Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent... (Meta-Analysis)
Meta-Analysis
The long-term efficacy and safety of apatinib are inferior to sorafenib in the first-line treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.
BACKGROUND
Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent years. For more than a decade, sorafenib has been the classic first-line treatment option for patients with advanced HCC. However, the results of clinical studies comparing the efficacy and safety of these 2 drugs are still controversial. Therefore, the aim of this meta-analysis is to evaluate the efficacy and safety of apatinib versus sorafenib as first-line treatment for advanced HCC.
METHODS
Up to August 14, 2023, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and clinical studies of experimental group (apatinib or apatinib plus transarterial chemoembolization [TACE]) versus control group (sorafenib or sorafenib plus TACE) in the first-line treatment of advanced HCC were included. Two researchers evaluated the quality of the included studies and extracted the data. Revman 5.4 software was used for meta-analysis.
RESULTS
A total of 12 studies involving 1150 patients were included. Five studies are apatinib alone versus sorafenib alone, and the other 7 studies are apatinib plus TACE versus sorafenib plus TACE. The results of the meta-analysis showed that compared with sorafenib alone, apatinib could improve (OR = 3.06, 95%CI: 1.76-5.31), had no advantage in improving DCR (OR = 1.52, 95%CI: 0.86-2.68) and prolonging PFS (HR = 1.35, 95%CI: 0.94-1.96), and was significantly worse in prolonging OS (HR = 1.43, 95%CI: 1.08-1.88). Similarly, apatinib plus TACE was inferior to sorafenib plus TACE in prolonging OS (HR = 1.15, 95%CI: 1.03-1.28), although it improved ORR (OR = 1.49, 95%CI: 1.03-2.16). In terms of adverse drug events, the overall incidence of adverse events, and the incidence of drug reduction and discontinuation in the experimental group were significantly higher than those in the control group (P < .05). The incidence of hypertension, proteinuria, and oral mucositis in the experimental group was significantly higher than that in the control group (P < .05).
CONCLUSION
In the setting of first-line treatment of advanced HCC, apatinib has improved short-term efficacy (ORR) compared with sorafenib, but the safety and long-term efficacy of apatinib are inferior to sorafenib.
Topics: Humans; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Liver Neoplasms; Pyridines; Sorafenib
PubMed: 38241568
DOI: 10.1097/MD.0000000000036865 -
Renal Failure Dec 2024To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by... (Meta-Analysis)
Meta-Analysis
Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.
OBJECTIVE
To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.
METHODS
PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.
RESULTS
A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.
CONCLUSIONS
The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Drug Therapy, Combination; Angiotensin Receptor Antagonists; Astragalus Plant; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome; Creatinine; Glycated Hemoglobin; Proteinuria
PubMed: 38836372
DOI: 10.1080/0886022X.2024.2359033 -
Frontiers in Pharmacology 2024Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer...
Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.
Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis. An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses. This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517-0.731; 95% PI = 0.379-0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114-2.021; 95% PI = 0.218-10.346), fatigue (RR = 1.264, 95% CI = 1.141-1.400; 95% PI = 1.012-1.552), headache (RR = 1.868, 95% CI = 1.036-3.369; 95% PI = 0.154-22.642), anorexia (RR = 1.718, 95% CI = 1.320-2.235; 95% PI = 0.050-65.480), and hypertension (RR = 5.009, 95% CI = 1.103-22.744; 95% PI = 0.016-1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737-1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all < 0.05). Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.
PubMed: 38584601
DOI: 10.3389/fphar.2024.1372077