-
Frontiers in Immunology 2024Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing...
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
Topics: Humans; Programmed Cell Death 1 Receptor; Immunotherapy, Adoptive; Lymphoma; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Animals; Neoplasms; Combined Modality Therapy; Tumor Microenvironment; Antigens, Neoplasm; T-Lymphocytes
PubMed: 38799440
DOI: 10.3389/fimmu.2024.1389971 -
Viruses Apr 2024This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted... (Review)
Review
This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Hepatitis B virus; Adaptive Immunity; T-Lymphocytes, Regulatory; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Hepatitis B; Hepatitis B, Chronic; CD4-Positive T-Lymphocytes; T-Lymphocytes; Immunotherapy
PubMed: 38793588
DOI: 10.3390/v16050707 -
BMC Cancer May 2024Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN)...
BACKGROUND
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC.
METHODS
MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens.
RESULTS
Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics.
CONCLUSIONS
The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.
Topics: Humans; Cyclin-Dependent Kinase 4; Breast Neoplasms; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Female; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Receptors, Estrogen; Receptors, Progesterone; Progression-Free Survival
PubMed: 38783218
DOI: 10.1186/s12885-024-12269-8 -
Journal of Nuclear Medicine : Official... Jul 2024Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated... (Meta-Analysis)
Meta-Analysis
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated promising results on the utility of PSMA-targeted PET/CT imaging in RCC. This report aims to provide a systematic review and metaanalysis on the utility and detection rate of PSMA PET/CT imaging in staging or evaluation of primary RCC and restaging of metastatic or recurrent RCC. Searches were performed in PubMed, Embase, and abstract proceedings (last updated, August 2023). Studies that provided a lesion-level detection rate of PSMA radiotracers in staging or restaging of RCC were included in the metaanalysis. The overall pooled detection rate with a 95% CI was estimated, and subgroup analysis was performed when feasible. Nine studies comprising 152 patients (133 clear cell RCC [ccRCC], 19 other RCC subtypes) were included in the metaanalysis. The pooled detection rate of PSMA PET/CT in evaluation of primary or metastatic RCC was estimated to be 0.83 (95% CI, 0.67-0.92). Subgroup analysis showed a pooled PSMA detection rate of 0.74 (95% CI, 0.57-0.86) in staging or evaluation of primary RCC lesions and 0.87 (95% CI, 0.73-0.95) in restaging of metastatic or recurrent RCC. Analysis based on the type of radiotracer showed a pooled detection rate of 0.85 (95% CI, 0.62-0.95) for Ga-based PSMA tracers and 0.92 (95% CI, 0.76-0.97) for F-DCFPyL PET/CT. Furthermore, in metastatic ccRCC, the available data support a significantly higher detection rate for F-DCFPyL PET/CT than for conventional imaging modalities (2 studies). Our preliminary results show that PSMA PET/CT could be a promising alternative imaging modality for evaluating RCC, particularly metastatic ccRCC. Large prospective studies are warranted to confirm clinical utility in the staging and restaging of RCC.
Topics: Carcinoma, Renal Cell; Positron Emission Tomography Computed Tomography; Humans; Kidney Neoplasms; Neoplasm Staging; Glutamate Carboxypeptidase II; Antigens, Surface
PubMed: 38782453
DOI: 10.2967/jnumed.124.267417 -
Expert Review of Pharmacoeconomics &... Jun 2024This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2... (Review)
Review
Quality-adjusted life years for HER2-positive, early-stage breast cancer using trastuzumab-containing regimens in the context of cost-effectiveness studies: a systematic review.
INTRODUCTION
This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs).
METHODS
A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison.
RESULTS
Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations.
CONCLUSIONS
Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders.
REGISTRATION
PROSPERO ID: CRD42021259826.
Topics: Humans; Cost-Benefit Analysis; Breast Neoplasms; Trastuzumab; Quality-Adjusted Life Years; Female; Receptor, ErbB-2; Quality of Life; Antineoplastic Agents, Immunological; Neoplasm Staging; Developed Countries
PubMed: 38738869
DOI: 10.1080/14737167.2024.2352006 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
International Journal of Molecular... May 2024V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose... (Meta-Analysis)
Meta-Analysis
V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the B7H4 prognostic value in solid cancers. Three databases were searched for relevant articles. The main endpoints were overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Appropriate hazard ratios (HRs) were pooled. The R studio software (version 4.0.3) was used for data analysis. Thirty-one studies met the inclusion criteria. High expression of B7H4 was associated with worse OS (HR = 1.52, 95% CI: 1.37-1.68) but not with DSS (HR = 1.14, 95% CI: 0.49-2.63), RFS (HR = 1.77, 95% CI: 0.75-4.18), DFS (HR = 1.29, 95% CI: 0.8-2.09), or PFS (HR = 1.71, 95% CI: 0.91-3.2) in patients with solid cancers. High expression of B7H4 is associated with a poorer prognosis in patients with solid cancers. B7H4 is a promising prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumourigenesis.
Topics: Humans; Neoplasms; V-Set Domain-Containing T-Cell Activation Inhibitor 1; Prognosis; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Disease-Free Survival
PubMed: 38732263
DOI: 10.3390/ijms25095045 -
Oral Oncology Jun 2024This systematic review and meta-analysis investigates the predictive and prognostic role of PD-L1 expression in treating head and neck squamous cell carcinoma (HNSCC).... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis investigates the predictive and prognostic role of PD-L1 expression in treating head and neck squamous cell carcinoma (HNSCC). Recognizing the importance of PD-L1 in patient response to treatment, the main objective was to assess its impact on overall survival and progression-free survival in HNSCC patients. A thorough search of databases such as PubMed, Scopus, and Web of Science from 2010 to 2022, along with relevant articles and references, yielded 120 studies. Of these, 7 met the criteria focusing on HNSCC patients, PD-L1 expression evaluation, and treatment with PD-1 or PD-L1 inhibitors. Data extraction followed PRISMA guidelines and involved independent review and consensus for discrepancies. The primary outcomes analyzed were overall survival and progression-free survival in relation to PD-L1 expression levels in patients undergoing immunotherapy.Theseven randomized controlled trials selected had a total of 4,477 participants. Results showed that patients with positive PD-L1 expression experienced improved overall survival when treated with PD-1 or PD-L1 inhibitors, particularly those with high PD-L1 expression. However, PD-L1 expression did not significantly affect progression-free survival. These findings suggest that PD-L1 expression can be a predictive marker for better overall survival in HNSCC patients treated with immunotherapy. However, its influence on progression-free survival remains unclear, indicating the need for further research.
Topics: Humans; B7-H1 Antigen; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; Biomarkers, Tumor; Immune Checkpoint Inhibitors
PubMed: 38729036
DOI: 10.1016/j.oraloncology.2024.106799 -
European Journal of Surgical Oncology :... Jul 2024Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER).
METHODS
A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity.
RESULTS
Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER.
CONCLUSION
This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.
Topics: Gallbladder Neoplasms; Humans; Risk Factors; Neoplasm Recurrence, Local; Carcinoembryonic Antigen; CA-19-9 Antigen; Lymphatic Metastasis; Neoplasm Staging
PubMed: 38718620
DOI: 10.1016/j.ejso.2024.108372 -
Oral Oncology Jun 2024Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has been undertaken for treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We conducted a meta-analysis to provide a more precise assessment of the efficacy and safety of this integrated approach in managing R/M HNSCC.
METHODS
A systematic exploration encompassing PubMed, Embase, the Cochrane Library, and Web of Science databases was undertaken to figure out relevant studies. It was attempted to analyze critical endpoints, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) utilizing a random-effects model.
RESULTS
Eleven studies, encompassing 413 patients, were analyzed. The combined data revealed an ORR of 41 % (95 % CI: 34-49 %), a DCR of 67 % (95 % CI: 51-83 %), a median PFS of 5.87 months (95 % CI: 3.90-7.85), and a median OS of 9.63 months (95 % CI: 6.78-12.49). Furthermore, the rates for 1-year PFS and OS were 45 % (95 % CI: 27-64 %) and 65 % (95 % CI: 49-81 %), respectively. The occurrence of grade 3 or higher adverse events related to the drugs was 20 % (95 % CI: 10-30 %). Subgroup analysis within the tyrosine kinase inhibitor (TKI) group revealed an ORR of 47 % (95 % CI: 39 %-55 %) and a DCR of 67 % (95 % CI: 46 %-88 %).
CONCLUSIONS
In summary, combining VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors shows considerable effectiveness with manageable side effects in cases with R/M HNSCC.
SYSTEMATIC REVIEW REGISTRATION
Registered with the International Prospective Register of Systematic Reviews, identifier CRD42023486345.
Topics: Humans; Vascular Endothelial Growth Factor A; Receptors, Vascular Endothelial Growth Factor; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Head and Neck Neoplasms; Male; Female
PubMed: 38714115
DOI: 10.1016/j.oraloncology.2024.106814