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BMC Cancer Nov 2023Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell... (Meta-Analysis)
Meta-Analysis
PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear.
METHOD
We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I statistics. R, version 4.2.3, was used for statistical analyses.
RESULTS
A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23-0.44; p < 0.001) and overall survival (OS) at 30 months (RR 3.13; 95% CI 1.26-7.78; p = 0.01) were significant in favor of the PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel group in the mismatch repair-deficient subgroup. However, there were no significant differences in the mismatch repair-proficient subgroup for PFS (HR 0.74; 95% CI 0.50-1.08; p = 0.117) or OS at 30 months (RR 2.24; 95% CI 0.79-6.39; p = 0.13).
CONCLUSION
Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer, with a significant benefit in the mismatch repair-deficient and high microsatellite instability population.
Topics: Female; Humans; Carboplatin; Paclitaxel; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; Endometrial Neoplasms; B7-H1 Antigen; Lung Neoplasms
PubMed: 38031003
DOI: 10.1186/s12885-023-11654-z -
Current Oncology (Toronto, Ont.) Nov 2023: The purpose of this study was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for the treatment of... (Meta-Analysis)
Meta-Analysis Review
: The purpose of this study was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for the treatment of metastatic urothelial carcinoma (mUC). A literature search was conducted of PubMed, EMBASE, and the Cochrane Library and was limited to the English literature. Randomized controlled trials (RCTs) published up to July 2022 were considered for inclusion. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥ 3 treatment-related AEs (TRAE). Subgroup analysis was performed based on the PD-L1 expression status, and the differences between first- and second-line PD-1/PD-L1 inhibitors were estimated. We included five RCTs comprising 3584 patients in the analysis. Compared with chemotherapy alone, the use of PD-1/PD-L1 inhibitors as monotherapy did not significantly prolong OS [hazard ratios (HR), 0.90; 95% CI, 0.81-1.00] or PFS (HR, 1.12; 95% CI, 0.95-1.32). However, the PD-1/PD-L1 inhibitor combined with chemotherapy significantly improved both OS (HR, 0.85; 95% CI, 0.74-0.96) and PFS (HR, 0.80; 95% CI, 0.71-0.90). Additionally, subgroup analysis showed that in mUC with PD-L1 expression ≥ 5%, treatment with the PD-1/PD-L1 inhibitor alone did not reduce the risk of death. Safety analysis showed that the PD-1/PD-L1 inhibitor alone did not significantly increase the incidence rates of grade ≥ 3 TRAEs. The results show that use of the PD-1/PD-L1 inhibitor alone as first-line treatment is similar to chemotherapy in terms of both survival and response rates. However, the PD-1/PD-L1 inhibitor plus chemotherapy has a significant benefit in terms of PFS or OS. Nonetheless, more RCTs are warranted to evaluate efficiency and safety in the combination regimen of chemotherapy and PD-1/PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Progression-Free Survival; Carcinoma
PubMed: 37999142
DOI: 10.3390/curroncol30110722 -
Clinical Oncology (Royal College of... Jan 2024The aim of this systematic review with meta-analysis was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Checkpoint Inhibitors in Patients With Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Meta-analysis.
AIMS
The aim of this systematic review with meta-analysis was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC).
MATERIALS AND METHODS
We searched PubMed, Embase and Cochrane Library until 1 July 2022 for mCRPC trials testing PD-1/PD-L1 checkpoint inhibitors. We measured the efficacy and safety using overall survival, progression-free survival (PFS), overall response rates (ORR), prostate-specific antigen (PSA) response rate or treatment-related adverse events (TRAEs). When possible, data were meta-analysed.
RESULTS
Thirteen studies involving 2533 participants were included in this meta-analysis. The pooled hazard ratio for overall survival was 0.81 (95% confidence interval 0.42-1.20, I = 80.3%, P<0.001) and for PFS was 0.65 (95% confidence interval 0.38-0.92, I = 72.2%, P = 0.013). Furthermore, better ORR (relative risk = 2.77, 95% confidence interval 1.25-6.13, I = 0%, P = 0.699) was found in PD-L1-expressing tumours. However, no statistical trends between PD-L1 status on PSA response rate (relative risk = 0.79, 95% confidence interval 0.5-1.25, I = 0%, P = 0.953) and tumour mutational burden on ORR (relative risk = 2.53, 95% confidence interval 0.49-13.12, I = 74.5%, P = 0.02) were observed. The pooled proportions of TRAEs and ≥ grade 3 TRAEs were 85.1% (95% confidence interval = 71.7-98.5%) and 31.6% (95% confidence interval = 18.9-44.4%), respectively.
CONCLUSIONS
This meta-analysis showed that among selected populations of men with mCRPC, anti-PD-1/PD-L1 combination treatment may significantly increase the PFS benefits. However, overall survival in mCRPC warrants further testing.
Topics: Male; Humans; Programmed Cell Death 1 Receptor; Prostatic Neoplasms, Castration-Resistant; B7-H1 Antigen; Prostate-Specific Antigen; Ligands; Immune Checkpoint Inhibitors
PubMed: 37993317
DOI: 10.1016/j.clon.2023.11.034 -
Drug Safety Dec 2023Immune checkpoint inhibitors (ICIs) have shown efficacy in tumor therapy. However, the risk of pulmonary toxicity from ICI-based treatment regimens remains unknown. We...
Immune checkpoint inhibitors (ICIs) have shown efficacy in tumor therapy. However, the risk of pulmonary toxicity from ICI-based treatment regimens remains unknown. We searched multiple databases and clinical trial websites from January 2015 to December 2021 and summarized the pulmonary toxicity profile and risk ranking of ICI-based treatments in cancer patients. We included a Phase III randomized clinical trial (RCT) in which the treatment group received at least one ICI and experienced pulmonary adverse events (PAEs). Our study, which included 104 RCTs, found the highest incidence of grades 1-2 and 3-5 treatment-associated PAEs (Tr-PAEs) in programmed death 1 (PD-1)+ chemotherapy and PD-1+ cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), respectively. The first incidence rates of grades 1-2 and 3-5 immune-mediated PAEs (Im-PAEs) were PD1+CTLA-4+ chemotherapy and PD-L1 + CTLA4, respectively. Cytotoxic T lymphocyte-associated antigen 4 + chemotherapy regimen and PD-L1+ targeted therapy drug (TTD)+ chemotherapy regimen had the highest risk of developing grades 1-2 and 3-5 Tr-PAEs. Programmed death-L1+ CTLA-4 has a higher risk of grade 3-5 Tr-PAEs than PD-L1. The risk of grade 1-2 pulmonary toxicity was significantly different in the high-dose and low-dose groups of nivolumab and atezolizumab. Nivolumab and atezolizumab induced dose-dependent grade 1-2 pulmonary toxicity. Among single-agent regimens, PD-1 showed the greatest grade 1-2 pulmonary toxicity. Programmed death-L1+ TTD+ chemotherapy showed the greatest grade 3-5 pulmonary toxicity in combination therapy. PD-L1+ TTD+ chemotherapy was associated with a higher risk of grade 3-5 Tr-PAEs and a lower risk of Im-PAEs. We recommend a targeted approach to managing PAE.
Topics: Humans; Nivolumab; CTLA-4 Antigen; Immune Checkpoint Inhibitors; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 37934397
DOI: 10.1007/s40264-023-01357-6 -
World Journal of Surgical Oncology Nov 2023The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors.
METHODS
This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software.
RESULTS
A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3-4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3-4 adverse events in patients (P < 0.05).
CONCLUSIONS
As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3-4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.
Topics: Humans; Immune Checkpoint Inhibitors; Neoadjuvant Therapy; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Neoplasms; Multicenter Studies as Topic
PubMed: 37926852
DOI: 10.1186/s12957-023-03212-5 -
Expert Review of Anticancer Therapy 2023Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs.
METHODS
We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS).
RESULTS
Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; <0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (<0.001, = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, <0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, <0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable.
CONCLUSION
Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS ( < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.
Topics: Humans; Melanoma; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Skin Neoplasms; CTLA-4 Antigen
PubMed: 37908134
DOI: 10.1080/14737140.2023.2278509 -
International Journal of Molecular... Sep 2023The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and... (Review)
Review
The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin's lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy.
Topics: Humans; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Programmed Cell Death 1 Receptor; Neoplasm Recurrence, Local; Hematologic Neoplasms; Immunotherapy, Adoptive; T-Lymphocytes
PubMed: 37834228
DOI: 10.3390/ijms241914780 -
Frontiers in Immunology 2023Accurate prediction of efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors is of critical importance. To address this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate prediction of efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors is of critical importance. To address this issue, a network meta-analysis (NMA) comparing existing common measurements for curative effect of PD-1/PD-L1 monotherapy was conducted.
METHODS
We searched PubMed, Embase, the Cochrane Library database, and relevant clinical trials to find out studies published before Feb 22, 2023 that use PD-L1 immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), microsatellite instability (MSI), multiplex IHC/immunofluorescence (mIHC/IF), other immunohistochemistry and hematoxylin-eosin staining (other IHC&HE) and combined assays to determine objective response rates to anti-PD-1/PD-L1 monotherapy. Study-level data were extracted from the published studies. The primary goal of this study was to evaluate the predictive efficacy and rank these assays mainly by NMA, and the second objective was to compare them in subgroup analyses. Heterogeneity, quality assessment, and result validation were also conducted by meta-analysis.
FINDINGS
144 diagnostic index tests in 49 studies covering 5322 patients were eligible for inclusion. mIHC/IF exhibited highest sensitivity (0.76, 95% CI: 0.57-0.89), the second diagnostic odds ratio (DOR) (5.09, 95% CI: 1.35-13.90), and the second superiority index (2.86). MSI had highest specificity (0.90, 95% CI: 0.85-0.94), and DOR (6.79, 95% CI: 3.48-11.91), especially in gastrointestinal tumors. Subgroup analyses by tumor types found that mIHC/IF, and other IHC&HE demonstrated high predictive efficacy for non-small cell lung cancer (NSCLC), while PD-L1 IHC and MSI were highly efficacious in predicting the effectiveness in gastrointestinal tumors. When PD-L1 IHC was combined with TMB, the sensitivity (0.89, 95% CI: 0.82-0.94) was noticeably improved revealed by meta-analysis in all studies.
INTERPRETATION
Considering statistical results of NMA and clinical applicability, mIHC/IF appeared to have superior performance in predicting response to anti PD-1/PD-L1 therapy. Combined assays could further improve the predictive efficacy. Prospective clinical trials involving a wider range of tumor types are needed to establish a definitive gold standard in future.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Network Meta-Analysis; Prospective Studies; Biomarkers, Tumor; Gastrointestinal Neoplasms
PubMed: 37822932
DOI: 10.3389/fimmu.2023.1265202 -
Cancer Medicine Oct 2023Immune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
Immune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from different studies were controversial.
METHODS
Online databases were searched for randomized clinical trials (RCTs) evaluating ICIs for R/M HNSCC. The characteristics of the studies and the results of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), treatment-related adverse events (TRAEs) were extracted.
RESULTS
A total of 4936 patients from eight studies were included. Anti-PD1/PDL1 monotherapy significantly improved OS in total population (hazard ratio, HR, 0.87, 95% CI, 0.79-0.95, p = 0.003) and PD-L1 high expression patients (HR, 0.71, 95% CI, 0.55-0.90, p = 0.006) with significant lower incidence of any grade TRAEs (odds ratio, OR, 0.16, 95% CI, 0.07-0.37, p < 0.00001) and Grades 3-5 TRAEs (OR, 0.18, 95% CI, 0.10-0.33, p < 0.0001) compared with standard of care (SOC); however, the pooled results of PFS and ORR were not significant different. PD1/PDL1 inhibitors plus CTLA4 inhibitors did not improve OS, PFS, ORR compared with SOC or ICIs monotherapy; however, the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy (OR, 1.80, 95% CI, 1.34-2.41, p = 0.0001).
CONCLUSIONS
Anti-PD1/PDL1 monotherapy could improve OS for R/M HNSCC with significant lower incidence of TRAEs compared with SOC. PD1/PDL1 inhibitors plus CTLA4 inhibitors showed no more benefit compared with both SOC and ICIs monotherapy, but the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; CTLA-4 Antigen; Randomized Controlled Trials as Topic; Carcinoma; Head and Neck Neoplasms
PubMed: 37814950
DOI: 10.1002/cam4.6564 -
British Journal of Haematology Dec 2023
Meta-Analysis
Topics: Humans; Receptors, Chimeric Antigen; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Burkitt Lymphoma; Immunotherapy, Adoptive; Antigens, CD19
PubMed: 37814795
DOI: 10.1111/bjh.19149