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Pharmacological Research Feb 2024To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors.
METHODS
We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest.
RESULTS
18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRAS-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77).
CONCLUSIONS
This study provided a comprehensive understanding of the efficacy and safety of KRAS inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRAS inhibitor treatment.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Proto-Oncogene Proteins p21(ras); NF-E2-Related Factor 2; Carcinoma, Non-Small-Cell Lung; Mutation; Lung Neoplasms
PubMed: 38185210
DOI: 10.1016/j.phrs.2024.107060 -
Reviews in Endocrine & Metabolic... Dec 2023Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain.
OBJECTIVE
This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC.
METHODS
Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model.
RESULTS
A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR.
CONCLUSIONS
Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.
Topics: Humans; Middle Aged; Prognosis; Prospective Studies; Lymphocytes; Inflammation; Thyroid Neoplasms
PubMed: 37828383
DOI: 10.1007/s11154-023-09845-x -
European Journal of Cancer (Oxford,... Sep 2023The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and ii) whether anthracyclines could be excluded.
METHODS
A systematic literature search in Medline, Embase and Web of Science databases was performed. Studies had to satisfy the following criteria: i) randomised controlled trials (RCTs), ii) enroled patients treated preoperatively for HER2-positive BC (breast cancer), iii) at least one treatment group received an anti-HER2 agent, iv) available information of any efficacy end-point and v) published in English. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR), event-free survival (EFS) and overall survival (OS) were the efficacy end-points of interest, and selected safety end-points were also analysed.
RESULTS
A total of 11,049 patients with HER2-positive BC (46 RCTs) were included in the network meta-analysis, and 32 different regimens were evaluated. Dual anti-HER2-therapy, with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab and chemotherapy in terms of pCR, EFS and OS. However, a higher risk of cardiotoxicity was observed with dual anti-HER2-therapy. Anthracycline-based chemotherapy was not associated with better efficacy outcomes in comparison with non-anthracycline-based chemotherapy. In anthracycline-free regimens, the addition of carboplatin presented numerically better efficacy outcomes.
CONCLUSION
Dual HER2 blockade with chemotherapy is the recommended choice as neoadjuvant therapy for HER2-positive breast cancer, preferably by omitting anthracyclines in favour of carboplatin.
Topics: Humans; Female; Neoadjuvant Therapy; Carboplatin; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Antibiotics, Antineoplastic; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37142539
DOI: 10.1016/j.ejca.2023.03.042 -
Japanese Journal of Clinical Oncology Jul 2023We performed a meta-analysis to assess the efficacy and safety of T-DXd in the treatment of HER2-expressing solid tumours. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed a meta-analysis to assess the efficacy and safety of T-DXd in the treatment of HER2-expressing solid tumours.
METHODS
We systematically searched PubMed, Web of Science, Embase and the Cochrane Library and collected studies published before March 17, 2023, on T-DXd for HER2-expressing tumours for a meta-analysis. We performed a subgroup analysis based on the different cancer types and the doses used.
RESULTS
There were 11 studies including 1349 HER2-expressing patients in this meta-analysis. The pooled ORR was 47.91%, and the pooled DCR was 87.01%. The mPFS and mOS combined were 9.63 and 10.71 months, respectively. The most common adverse reactions in grades 1-2 were decreased appetite (49.3%) and vomiting (43.0%). The netropemia (31.2%) and leukopenia (31.2%) were the most common grade 3 and higher adverse reactions. Subgroup analysis showed that breast cancer had the best ORR and DCR, with 66.96 and 96.52%, respectively.
CONCLUSIONS
Overall, the efficacy of T-DXd in treating HER2-expressing solid tumours is encouraging, especially breast and non-small cell lung cancers, and has an acceptable safety profile. However, concerns remain about potentially serious treatment adverse events (e.g. interstitial lung disease/pneumonia). More well-designed, large-scale randomized controlled trials are needed to demonstrate our study.
Topics: Female; Humans; Breast Neoplasms; Camptothecin; Immunoconjugates; Lung Neoplasms; Receptor, ErbB-2; Trastuzumab
PubMed: 37114934
DOI: 10.1093/jjco/hyad036 -
ESMO Open Aug 2023Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis.
MATERIALS AND METHODS
A systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777).
RESULTS
Among 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found.
CONCLUSIONS
Compared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Disease-Free Survival; Progression-Free Survival; Proportional Hazards Models
PubMed: 37413762
DOI: 10.1016/j.esmoop.2023.101592 -
Asian Pacific Journal of Cancer... Aug 2023Tumor budding (TB) has been investigated in several types of solid tumors. In oral cancer, studies show its association with survival. However, for its implementation in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tumor budding (TB) has been investigated in several types of solid tumors. In oral cancer, studies show its association with survival. However, for its implementation in routine histological analyses, results with a high certainty of evidence are needed. Therefore, the aim of this systematic review is to explore the association between tumor budding and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in oral cancer.
METHODS
A search was performed in Embase, PubMed, Scopus, Livivo, Web of Science, and Google Scholar. We adopted the following inclusion criteria: studies that evaluate tumor budding in oral cancer, that investigate survival, and presenting cohort design. We excluded reviews and studies without hazard-ratio (HR) data.
RESULTS
This systematic review included 22 studies and showed an association between TB and survival. High-grade TB is associated with a worse OS in univariate analysis (HR = 3.11; 95% CI: 2.06-4.69, p<0.01) and multivariate analysis (HR = 2.62; 95% CI: 1.64-4.20, p<0.01); with a poorer DSS in univariate (HR = 2.43; 95% CI: 1.94-3.03, p<0.01) and multivariate analysis (HR = 2.01; 95% CI: 1.43-2.83, p< 0.01); and with a worse DFS in univariate (HR = 1.94; 95% CI: 1.44-2.62, p<0.01) and multivariate analysis (HR = 2.15; 95% CI: 1.31-3.53, p< 0.01). Sensitivity analysis showed that the results are robust, and no significant publication bias was identified in univariate analysis for DFS (Egger's test: p = 0.94). The certainty of the evidence was graded as low or very low.
CONCLUSION
Our findings indicate that TB is an independent prognostic factor of OS, DSS, and DFS in oral cancer. However, further studies are needed to increase the certainty of the evidence.
Topics: Humans; Mouth Neoplasms; Disease-Free Survival; Progression-Free Survival; Multivariate Analysis; PubMed
PubMed: 37642041
DOI: 10.31557/APJCP.2023.24.8.2565 -
BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7 -
Human Vaccines & Immunotherapeutics Dec 2024Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after... (Meta-Analysis)
Meta-Analysis
Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%-64.5% = 18) and 90.2% (95% CI 80.9%-96.6% = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%-90.7% = 50) and 98.9% (95% CI 97.6%-99.7% = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%-95.9% = 21) and 99.8% (95% CI 98.1%-100.0% = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.
Topics: Humans; Neoplasms; COVID-19 Vaccines; COVID-19; Antibodies, Viral; Seroconversion; SARS-CoV-2; Vaccination
PubMed: 38785118
DOI: 10.1080/21645515.2024.2357424 -
Immunopharmacology and Immunotoxicology Jun 2024The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors.
METHOD
By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures.
RESULTS
A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities.
CONCLUSIONS
Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.
Topics: Humans; Antineoplastic Agents; Neoplasms; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Treatment Outcome
PubMed: 38627024
DOI: 10.1080/08923973.2024.2344153 -
Academic Radiology Dec 2023More pulmonary nodules (PNs) have been detected with the wide application of computed tomography (CT) in lung cancer screening. Radiomics is a noninvasive approach to... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
More pulmonary nodules (PNs) have been detected with the wide application of computed tomography (CT) in lung cancer screening. Radiomics is a noninvasive approach to predict the malignancy of PNs. We aimed to systematically evaluate the methodological quality of the eligible studies regarding CT-based radiomics models in predicting the malignancy of PNs and evaluate the model performance of the available studies.
MATERIALS AND METHODS
PubMed, Embase, and Web of Science were searched to retrieve relevant studies. The methodological quality of the included studies was assessed using the Radiomics Quality Score (RQS) and Prediction model Risk of Bias Assessment Tool. A meta-analysis was conducted to evaluate the performance of CT-based radiomics model. Meta-regression and subgroup analyses were employed to investigate the source of heterogeneity.
RESULTS
In total, 49 studies were eligible for qualitative analysis and 27 studies were included in quantitative synthesis. The median RQS of 49 studies was 13 (range -2 to 20). The overall risk of bias was found to be high, and the overall applicability was of low concern in all included studies. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.86 95% confidence interval (CI): 0.79-0.91, 0.84 95% CI: 0.78-0.88, and 31.55 95% CI: 21.31-46.70, respectively. The overall area under the curve was 0.91 95% CI: 0.89-0.94. Meta-regression showed the type of PNs on heterogeneity. CT-based radiomics models performed better in studies including only solid PNs.
CONCLUSION
CT-based radiomics models exhibited excellent diagnostic performance in predicting the malignancy of PNs. Prospective, large sample size, and well-devised studies are desired to verify the prediction capabilities of CT-based radiomics model.
Topics: Humans; Lung Neoplasms; Early Detection of Cancer; Prospective Studies; Multiple Pulmonary Nodules; Odds Ratio
PubMed: 37385850
DOI: 10.1016/j.acra.2023.05.026