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Cancer Control : Journal of the Moffitt... 2024Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This study aimed to investigate the effect of the addition of ICI to multi-TKIs on the profile of treatment-related adverse events.
METHODS
An electronic database search was performed using PubMed and Web of Science to identify published clinical studies on multi-TKI monotherapy and multi-TKI plus ICI combination therapy from July 20, 2005 to July 1, 2023. The incidence rate of common adverse events caused by multi-TKI monotherapy and multi-TKI plus ICI combination therapy was obtained and compared from the viewpoints of (1) relative risk for the combination therapy vs sunitinib, (2) adverse event incidence rate by clinical trial, and (3) pooled incidence rate. The quality of the evidence was assessed with the Cochrane risk of bias tool. Meta-analysis used random effects models.
RESULTS
This systematic review identified 83 clinical studies involving 7951 patients. The combination therapy of multi-TKI and ICI was associated with an increased risk of diarrhea (relative risk [RR]: 1.24, 95% confidence interval [CI]: 1.15-1.33, < .001), hypothyroidism (RR: 1.44, 95% CI: 1.11-1.87, = .0064) and rash (RR: 1.71, 95% CI: 1.18-2.47, = .0045) compared with multi-TKI monotherapy. The addition of ICI was suggested to decrease the risk of adverse events related to performance status.
CONCLUSION
Our study identified an increased risk of treatment-related adverse events associated with multi-TKI plus ICI combination therapy. This would help optimize the management of toxicities caused by multi-TKI plus ICI combination therapy.
Topics: Humans; Immune Checkpoint Inhibitors; Tyrosine Kinase Inhibitors; Combined Modality Therapy; Protein Kinase Inhibitors; Databases, Factual
PubMed: 38581169
DOI: 10.1177/10732748241244586 -
Clinical Breast Cancer Jul 2024Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the... (Meta-Analysis)
Meta-Analysis
Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Neoadjuvant Therapy; Poly(ADP-ribose) Polymerase Inhibitors; Receptor, ErbB-2; Treatment Outcome
PubMed: 38580572
DOI: 10.1016/j.clbc.2024.02.020 -
Frontiers in Pharmacology 2024This study aimed to assess the efficacy and safety of saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI)....
This study aimed to assess the efficacy and safety of saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, < 0.05], cardiac troponin T [MD = -3.01, < 0.05], and cardiac troponin I [MD = -10.72, < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, < 0.05], left ventricular ejection fraction [MD = 5.91, < 0.05], left ventricular end-diastolic dimension [MD = -3.08, < 0.05], and cardiac output [MD = 0.53, < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, < 0.05], tumor necrosis factor-α [MD = -6.47, < 0.05], interleukin-6 [MD = -24.46, < 0.05], and pentraxin-3 [MD = -2.26, < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, < 0.05] and increased nitric oxide [MD = 1.33, < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, < 0.05]; (10) no significant difference in adverse events [OR = 1.00, = 1.00]. This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. : (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).
PubMed: 38576488
DOI: 10.3389/fphar.2024.1353662 -
Systematic Reviews Apr 2024Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of... (Meta-Analysis)
Meta-Analysis
Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis.
BACKGROUND
Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.
METHODS
A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran's Q-test and I test statistics.
RESULTS
In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).
CONCLUSIONS
In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021246295.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Class I Phosphatidylinositol 3-Kinases; Genetic Variation; Ki-67 Antigen; Receptor, ErbB-2; Receptors, Estrogen; Taxoids; Triple Negative Breast Neoplasms
PubMed: 38576013
DOI: 10.1186/s13643-024-02520-5 -
Respiratory Investigation May 2024The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially... (Meta-Analysis)
Meta-Analysis
Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.
BACKGROUND
The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD.
METHODS
We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model.
RESULTS
Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection.
CONCLUSIONS
We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Tyrosine Kinase Inhibitors; Quality of Life; Protein Kinase Inhibitors; ErbB Receptors; Lung Diseases, Interstitial; Risk Factors; Antineoplastic Agents; Observational Studies as Topic
PubMed: 38569441
DOI: 10.1016/j.resinv.2024.03.007 -
The Journal of Experimental Medicine Jun 2024Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered...
Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.
Topics: Humans; Autoimmunity; Colitis; Hypersensitivity; Inflammation; Dermatitis; Janus Kinase 1
PubMed: 38563820
DOI: 10.1084/jem.20232387 -
Clinical Lung Cancer Jun 2024A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure... (Review)
Review
A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure (HF) in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR) TKIs. Of 296 identified publications, 95 met eligibility criteria and were abstracted for QTp/TdP and HF outcomes (QTp/TdP: 83 publications, including 5 case study publications; HF: 79 publications, including 6 case study publications [involving 8 patients]). QTp incidence ranged from 0% to 27.8% in observational studies and from 0% to 11% in clinical trials, with no deaths due to QTp. There were no TdP events or deaths due to TdP. The incidence of HF ranged from 0% to 8%, and HF mortality rates ranged from 0% to 4%. Patients receiving treatment with EGFR TKIs should be monitored for signs of QTp, TdP, and HF per prescribing information. Standardized definitions and methods to improve monitoring of QTp, TdP, and HF-related events are needed in patients with NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Heart Failure; Lung Neoplasms; ErbB Receptors; Torsades de Pointes; Protein Kinase Inhibitors; Long QT Syndrome; Incidence; Tyrosine Kinase Inhibitors
PubMed: 38553324
DOI: 10.1016/j.cllc.2024.02.005 -
Expert Review of Anticancer Therapy May 2024To provide a more comprehensive understanding of the efficacy and safety profile of cabozantinib versus placebo in malignant tumors, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Comparative Study Review
OBJECTIVES
To provide a more comprehensive understanding of the efficacy and safety profile of cabozantinib versus placebo in malignant tumors, we conducted a systematic review and meta-analysis. This involved analyzing a collection of published randomized controlled trials to assess the outcomes.
METHODS
We used RevMan5.3 software to evaluate the outcomes of the collected studies. The primary outcome we focused on was progression-free survival (PFS), and the secondary outcomes included overall survival (OS) and disease control rate (DCR).
RESULTS
Our findings revealed that compared to placebo, cabozantinib significantly extended the PFS of patients [hazard ratios (HR) 0.37, 95% confidence intervals (CI): 0.32, 0.43, < 0.00001]. Additionally, cabozantinib improved the OS of patients [HR 0.78, 95%CI: 0.68, 0.91, = 0.002]. While it is important to note that cabozantinib was associated with a higher likelihood of causing digestive, cutaneous, and cardiovascular related adverse events [relative risk (RR) 4.40, 95% CI: 3.10, 6.25, < 0.00001].
CONCLUSION
Based on our analysis, cabozantinib significantly prolonged the PFS and OS of patients with malignant tumors ( < 0.01). We recommend the use of cabozantinib in treating advanced malignant tumors. However, it is important to continuously monitor and manage the drug-related adverse events.
REGISTRATION
PROSPERO (No. CRD42023449261).
Topics: Humans; Pyridines; Anilides; Antineoplastic Agents; Neoplasms; Randomized Controlled Trials as Topic; Progression-Free Survival; Survival Rate; Protein Kinase Inhibitors; Disease-Free Survival
PubMed: 38551185
DOI: 10.1080/14737140.2024.2337266 -
International Journal of Cardiology.... Jun 2024In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of... (Review)
Review
In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of sleep disorder in patients with cardiovascular disease (CVD). After searching PubMed and Embase, 78 articles were selected for this review. This review discusses the bidirectional relationship between CVD and sleep disorders. Sleep impairment is highly prevalent in patients with CVD and mainly involves insomnia and sleep-breathing disorders. Several valuable biomarkers could be implicated in predicting sleep disorders in CVD patients, such as placental growth factor, vascular endothelial growth factor family, high sensitivity C-reactive protein, endoglin, fms-like tyrosine kinase-1, plasminogen activator inhibitor-1, erythropoietin. Moreover, non-drug therapies, namely physical exercise, cognitive behavioral therapy for insomnia (CBT-I), and continuous positive airway pressure benefit the prognosis of patients with CVD. In conclusion, this study highlights the importance of sleep quality, which is responsible for long- and short-term cardiac outcomes in patients with CVD.
PubMed: 38549735
DOI: 10.1016/j.ijcrp.2024.200257 -
Journal of Pediatric... 2024Pediatric oncology patients receive multiple modalities of therapy to treat their malignancies. These modalities have the potential for acute toxicity and late effects.... (Review)
Review
Evidence-Based Recommendations for Education Provided to Patients and Families Regarding the Adverse Events of ALK and MEK Inhibitors: A Systematic Review From the Children's Oncology Group.
Pediatric oncology patients receive multiple modalities of therapy to treat their malignancies. These modalities have the potential for acute toxicity and late effects. In the last decade, a new modality known as targeted biological therapy, has become an integral part of treatment for pediatric cancers. As targeted therapy use has increased, adverse events specific to these targeted agents have emerged, requiring a new effort focused on providing education to patients and families regarding how best to report, monitor, and manage these adverse events. A clinical question was developed to guide the systematic literature review. Anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinase kinase (MEK) inhibitors were selected for review due to their frequency of use in pediatric oncology. The search was conducted to identify relevant articles published between January 1, 2000 and May 5, 2020. Articles were screened by two team members for inclusion/exclusion criteria using the web-based systematic review tool, Rayyan. Twenty-seven articles met the eligibility criteria for inclusion and were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. Adverse events for ALK and MEK inhibitors included manifestations of the gastrointestinal, hematologic, dermatologic, musculoskeletal, neurological, cardiovascular, and ocular systems. Recommendations for patient/family education were made for ALK and MEK inhibitors based on the reported adverse events. Adverse events of ALK and MEK inhibitors differ from the more common adverse events experienced with conventional treatment modalities used in pediatric oncology. It is important for nurses to include information regarding potential adverse events in patient/family education for children receiving these targeted agents.
Topics: Child; Humans; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Antineoplastic Agents; Neoplasms; Mitogen-Activated Protein Kinase Kinases
PubMed: 38549368
DOI: 10.1177/27527530231206101