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Advances in Therapy May 2024Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During... (Review)
Review
INTRODUCTION
Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During the disease course, 25-50% of patients will develop BrMs. Despite available treatments, survival rates for patients with NSCLC and BrMs remain low, and their overall prognosis is poor. Even with newer agents for NSCLC, options for treating BrMs can be limited by their ineffective transport across the blood-brain barrier (BBB) and the unique brain tumor microenvironment. The presence of actionable genomic alterations (AGAs) is a key determinant of optimal treatment selection, which aims to maximize responses and minimize toxicities. The objective of this systematic literature review (SLR) was to understand the current landscape of the clinical management of patients with NSCLC and BrMs, particularly those with AGAs.
METHOD
A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant SLR was conducted to identify studies in patients with BrMs in NSCLC. Searches used the EMBASE and MEDLINE databases, and articles published between January 1, 2017 and September 26, 2022 were reviewed.
RESULTS
Overall, 179 studies were included in the SLR. This subset review focused on 80 studies that included patients with NSCLC, BrMs, and AGAs (19 randomized controlled trials [RCTs], two single-arm studies, and 59 observational studies). Sixty-four of the 80 studies reported on epidermal growth factor receptor (EGFR) mutations, 14 on anaplastic lymphoma kinase (ALK) alterations, and two on both alterations. Ninety-five percent of studies evaluated targeted therapy. All RCTs allowed patients with previously treated, asymptomatic, or neurologically stable BrMs; the percentage of asymptomatic BrMs varied across observational studies.
CONCLUSIONS
Although targeted therapies demonstrate systemic benefits for patients with NSCLC, BrMs, and AGAs, there remains a continued need for effective therapies to treat and prevent BrMs in this population. Increased BBB permeability of emerging therapies may improve outcomes for this population.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Brain Neoplasms; Lung Neoplasms; Genomics; Anaplastic Lymphoma Kinase; Mutation
PubMed: 38509433
DOI: 10.1007/s12325-024-02799-9 -
PharmacoEconomics May 2024Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR)...
Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice.
OBJECTIVE
The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models.
METHODS
Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework.
RESULTS
Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking.
CONCLUSIONS
Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.
Topics: Humans; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; ErbB Receptors; Lung Neoplasms; Models, Economic; Mutation; Protein Kinase Inhibitors
PubMed: 38489077
DOI: 10.1007/s40273-024-01362-2 -
European Journal of Cancer (Oxford,... May 2024Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival...
BACKGROUND
Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) EBC.
METHODS
A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2- EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted.
RESULTS
The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173-186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis.
CONCLUSIONS
These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2- EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2- EBC.
Topics: Adult; Humans; Female; Disease-Free Survival; Breast Neoplasms; Progression-Free Survival; Proportional Hazards Models; Chemotherapy, Adjuvant; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38460476
DOI: 10.1016/j.ejca.2024.113977 -
Journal of Orthopaedic Surgery and... Mar 2024Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to... (Meta-Analysis)
Meta-Analysis
Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.
BACKGROUND
Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals.
METHODS
A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1β, TNF-α, MMP3, and MMP13.
RESULTS
56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions.
CONCLUSIONS
Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier: CRD42023377228.
Topics: Animals; Humans; Osteoarthritis, Knee; Network Meta-Analysis; Janus Kinases; NF-kappa B; Phosphatidylinositol 3-Kinases; STAT Transcription Factors; Signal Transduction; Acupuncture Therapy; Models, Animal
PubMed: 38459553
DOI: 10.1186/s13018-024-04660-9 -
PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958 -
American Journal of Obstetrics &... Mar 2024In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite extensive research, available data on its effectiveness in predicting preeclampsia in twin pregnancies are limited and conflicting. This meta-analysis aimed to assess the diagnostic accuracy of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in distinguishing cases with preeclampsia in twin pregnancies from healthy controls.
DATA SOURCES
Studies that evaluated the use of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia were searched in PubMed, Embase, and Cochrane databases from inception to August 6, 2023, without language restriction.
STUDY ELIGIBILITY CRITERIA
The following population, exposure, comparators, outcomes, and study designs were included: women with twin pregnancies; an increased soluble fms-like tyrosine kinase 1 to placental growth factor ratio with preeclampsia as the outcome; women without preeclampsia; a 2 × 2 diagnostic table, diagnostic accuracy data, and the incidence of preeclampsia; and prospective cohort studies and observational comparative studies, respectively.
STUDY APPRAISAL AND SYNTHESIS METHODS
The quality of the included studies was evaluated. Key parameters, including the specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, were calculated using the random- and fixed-effects models. In addition, the area under the receiver operating characteristic curve and the summary receiver operating characteristic curve were evaluated.
RESULTS
A total of 7 studies were included, including 442 women with twin pregnancies (115 patients with preeclampsia and 327 controls without preeclampsia). The results highlighted the promising effectiveness of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia in twin pregnancies with a pooled specificity of 0.89 (95% confidence interval, 0.80-0.95), a sensitivity of 0.84 (95% confidence interval, 0.73-0.93), a positive likelihood ratio of 32.76 (95% confidence interval, 12.82-83.74), and a negative likelihood ratio of 0.03 (95% confidence interval, 0.01-0.08). The combined diagnostic odds ratio was 35.72 (95% confidence interval, 12.92-98.76), and the area under the receiver operating characteristic curve was 0.92.
CONCLUSION
These collective findings underscore the potential of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio as an accurate marker for identifying preeclampsia among women with twin pregnancies.
Topics: Female; Humans; Pregnancy; Placenta Growth Factor; Pre-Eclampsia; Pregnancy, Twin; Prospective Studies; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38401234
DOI: 10.1016/j.ajogmf.2024.101290 -
Medicine Feb 2024To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECT
To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM).
METHODS
Seven databases were systematically searched, spanning the interval from 2016 to August 2023. Randomized controlled trials (RCTS) comparing dorzagliatin with placebo for the treatment of T2DM were applicable for containing this study. The relevant data were extracted, and a meta-analysis was implemented using RevMan 5.4 software.
RESULTS
A total of 3 studies involving 1332 patients were included. We use glycated hemoglobin (HbA1c) levels as the major indicator of efficacy, FBG, 2h postprandial blood glucose, Homa-β and Homa-IR to be Secondary outcome measures. Compared with placebo group, dorzagliatin significantly reduced blood glucose levels as well as enhanced insulin resistance. In terms of safety, no serious adverse events occurred. However, lipid-related indicators, especially triglycerides levels, and the incidence of hypoglycemia were higher in patients in the dorzagliatin group compared with those in the control group, but the increase from baseline was mild.
CONCLUSIONS
Dorzagliatin exerted favorable effects in hypoglycemic control, effectively reduced the HbA1c, FBG, and 2h postprandial blood glucose levels in T2DM patients, stimulated the secretion of insulin during the initial phase, and exerted a consistent hypoglycemic effect. However, the incidence of adverse events such as elevated blood lipids and cardiovascular risk warrants further investigations through long-term clinical trials.
Topics: Humans; Glucokinase; Glycated Hemoglobin; Blood Glucose; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Pyrazoles
PubMed: 38394489
DOI: 10.1097/MD.0000000000036916 -
BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
Scientific Reports Feb 2024Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall... (Meta-Analysis)
Meta-Analysis
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.
Topics: Female; Humans; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor Proteins; Neutropenia; Purines; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38326452
DOI: 10.1038/s41598-024-53151-8 -
ESMO Open Feb 2024Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population.
PATIENTS AND METHODS
We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2).
RESULTS
Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35).
CONCLUSIONS
Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM.
TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Brain Neoplasms; Camptothecin; Receptor, ErbB-2; Immunoconjugates
PubMed: 38320430
DOI: 10.1016/j.esmoop.2024.102233