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Journal of Thoracic Oncology : Official... Jul 2021A series of randomized controlled trials have investigated different first-line immunotherapy combinations, but the optimal combination strategy is yet to be established. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A series of randomized controlled trials have investigated different first-line immunotherapy combinations, but the optimal combination strategy is yet to be established.
METHODS
We performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences. We included published and gray sources of randomized clinical trials comparing immunotherapy combinations with other treatments as first-line treatments for patients with advanced NSCLC. This study was registered in the Prospective Register of Systematic Reviews (CRD42020210501) to ensure transparency.
RESULTS
We analyzed a total of 16 studies involving 8278 patients and including 10 immunotherapy combinations. For patients without programmed death-ligand 1 (PD-L1) selection, pembrolizumab plus chemotherapy was found to be comparable with sintilimab plus chemotherapy in providing the best overall survival (OS) benefit (hazard ratio = 0.96, 95% confidence interval [CI]: 0.72-1.29). Furthermore, atezolizumab plus bevacizumab plus chemotherapy seemed to provide the best progression-free survival (hazard ratio = 0.45, 95% CI: 0.36-0.55) and the best objective response rate (OR = 0.23, 95% CI: 0.12-0.42). Subgroup analysis by PD-L1 suggested that nivolumab plus ipilimumab plus chemotherapy was associated with the best OS in patients with PD-L1 less than 1% and that pembrolizumab plus chemotherapy was associated with the best OS in patients with PD-L1 greater than or equal to 1%. Pembrolizumab and sintilimab were associated with relatively fewer grade greater than or equal to 3 adverse events when compared with other immunotherapies combined with chemotherapy.
CONCLUSIONS
Our results suggest that antiprogrammed death-1 combinations are associated with potentially higher survival outcomes than anti-PD-L1 combinations with comparable safety profiles. Moreover, pem-chemo and nivo-ipi-chemo seem to be superior first-line immunotherapy combinations for patients with advanced NSCLC with positive and negative PD-L1 expression, respectively. Although atezo-beva-chemo treatment provided the best progression-free survival and objective response rate, the addition of chemotherapy to immunotherapy would increase the toxicity, especially when antiangiogenesis drugs are simultaneously added.
Topics: B7-H1 Antigen; Bayes Theorem; Humans; Immunotherapy; Lung Neoplasms; Network Meta-Analysis
PubMed: 33839365
DOI: 10.1016/j.jtho.2021.03.016 -
Medicinal Research Reviews Jul 2021Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via... (Review)
Review
Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF-κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor-β, Wnt/β-catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N-acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti-inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.
Topics: Endometriosis; Female; Humans; Pharmaceutical Preparations; Phosphatidylinositol 3-Kinases; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 33948974
DOI: 10.1002/med.21802 -
Cancers Jun 2022Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive... (Review)
Review
Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women's life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.
PubMed: 35805007
DOI: 10.3390/cancers14133238 -
BMJ Clinical Evidence Apr 2007Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with... (Review)
Review
INTRODUCTION
Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early-stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression of early- or late-stage age-related macular degeneration; and exudative age-related macular degeneration? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiangiogenesis (using pegaptanib, ranibizumab, interferon alfa-2a, or anecortave acetate), antioxidant vitamins plus zinc, external beam radiation, laser treatment to drusen, photodynamic therapy with verteporfin, submacular surgery, thermal laser photocoagulation, transpupillary thermotherapy.
Topics: Choroidal Neovascularization; Humans; Macular Degeneration; Photochemotherapy; Ranibizumab; Visual Acuity
PubMed: 19454069
DOI: No ID Found -
Journal of Cancer 2019: Pancreatic cancer is a common digestive neoplasm with a high fatality rate. We performed this systematic review and meta-analysis of clinical randomized phase III... (Review)
Review
Efficacy and safety of gemcitabine plus anti-angiogenesis therapy for advanced pancreatic cancer: a systematic review and meta-analysis of clinical randomized phase III trials.
: Pancreatic cancer is a common digestive neoplasm with a high fatality rate. We performed this systematic review and meta-analysis of clinical randomized phase III trials to explore the efficacy and safety of gemcitabine plus anti-angiogenesis therapy versus gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. : We searched PubMed, Embase and the Cochrane Library to identify eligible studies. Data were collected for the period from January 1, 2000 to August 20, 2018. Hazard ratios (HRs) and odds ratios (ORs) were used as main evaluation parameters. : A total of eight eligible studies with 3,586 individuals were included in the present meta-analysis. The results showed that the combination of gemcitabine plus anti-angiogenesis therapy had a significant effect on progression-free survival (HR = 0.92, 95% CI: 0.86 - 1.00, = 0.04), but led to no significant difference in the overall survival (HR = 0.96, 95% CI: 0.88 - 1.05, = 0.38). In terms of safety, gemcitabine plus anti-angiogenesis therapy did not increase the rate of grade 3-4 common adverse effects except for hypertension. : Although gemcitabine plus anti-angiogenesis therapy might prolong the progression-free survival in locally advanced or metastatic pancreatic cancer, these successful results did not translate into a significant improvement in the overall survival or change in the clinical guidelines.
PubMed: 30854103
DOI: 10.7150/jca.26672 -
Frontiers in Pharmacology 2022Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in...
Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies.
Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. The inclusion criteria were as follows: prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints: progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs). Twenty three prospective studies comprising 1,856 patients with advanced NSCLC were included. The pooled ORR, median PFS and estimated overall survival were 39%, 6.8 months [95% confidence interval (CI), 5.53-8.13], and 18.6 months in the overall group. Similar ORR and median PFS with A + I + chemo versus A + I were observed in patients treated in first-line setting [59% and 9.47 months (95% CI, 6.45-12.49) versus 52% and 10.9 months (95% CI, 1.81-19.98), respectively]. We also observed improved ORR and mPFS with A + I + chemo versus A + I in subsequent-line setting [56% and 8.1 months (95% CI, 5.00-11.26) versus 22% and 5.1 months (95% CI, 4.01-6.15), respectively]. Efficacy of A + I + chemo therapy was evident across different PD-L1 subgroups, especially in patients with EGFR mutations [ORR: 59%; mPFS: 8.13 months (95% CI: 5.00-11.26)] or baseline liver metastases. The incidence of AEs with a major grade of ≥3 in the overall, A + I, and A + I + chemo groups were 4.1% vs. 5.5% vs. 3.4% for proteinuria, 13.7% vs. 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis. Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.
PubMed: 36034821
DOI: 10.3389/fphar.2022.920165 -
Integrative Cancer Therapies 2022Cancer is a major cause of morbidity and mortality worldwide and therefore there has been interest in discovering the phytoconstituents of medicinal plants exhibiting... (Review)
Review
Cancer is a major cause of morbidity and mortality worldwide and therefore there has been interest in discovering the phytoconstituents of medicinal plants exhibiting anticancer activities. L., commonly known as Noni, has shown anticancer properties in in vitro, in vivo, and in clinical studies. A systematic review was conducted to collate scientific evidence on the anticancer properties of using pre-determined keywords on 5 electronic databases: MEDLINE, CENTRAL, LILACS, Web of Science, and EBSCOHost. A total of 51 clinical and preclinical studies comprising 41 efficacy and 10 safety studies were included in this review. Our findings showed that demonstrated various anticancer properties in different cancer models, via multiple mechanisms including antitumor, antiproliferative, pro-apoptotic, antiangiogenesis, antimigratory, anti-inflammatory, and immunomodulatory activities. is deemed to be a potentially valuable medicinal plant in the treatment of cancer through its many intrinsic pathways. More well-designed and reported preclinical efficacy and safety studies are needed to allow for better translation into future clinical studies which could further substantiate the role of in cancer treatment.
Topics: Humans; Morinda; Antineoplastic Agents; Immunotherapy; Immunomodulation
PubMed: 36448674
DOI: 10.1177/15347354221132848 -
Frontiers in Immunology 2022Anti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given the scarce quantitative analyses of anti-PD1/PDL1 in aBTC, we thus did a meta-analysis to assess the benefits and risks of this emerging treatment strategy in patients with aBTC.
METHODS
PubMed, Embase, the Cochrane Library, Web of Science, and meeting resources were searched for relevant studies. The main endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), any-grade adverse events (AEs), and grade 3-4 AEs.
RESULTS
Twenty-eight studies with 1,338 participants were included. The best curative effect was found in the anti-PD1/PDL1 combined with anti-CTLA4 and chemotherapy group (mPFS: 12.4 months; mOS: 16.0 months; ORR: 45.1%; DCR: 95.0%), followed by the anti-PD1/PDL1 plus chemotherapy group (mPFS: 8.2 months; mOS: 14.8 months; ORR: 36.3%; DCR: 84.6%), the anti-PD1/PDL1 plus antiangiogenesis group (mPFS: 4.9 months; mOS: 10.2 months; ORR: 17.5%; DCR: 68.7%), the anti-PD1/PDL1 plus anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) group (mPFS: 2.9 months; mOS: 8.3 months; ORR: 9.9%; DCR: 36.8%), and the anti-PD1/PDL1 monotherapy group (mPFS: 2.5 months; mOS: 7.6 months; ORR: 6.8%; DCR: 34.7%). Compared with anti-PD1-containing regimens, anti-PDL1-containing regimens achieved preferable mPFS (11.1 vs. 3.8 months), mOS (12.2 vs. 9.8 months), and ORR (23.7% vs. 17.4%), despite a similar DCR (61.1% vs. 61.3%). The mPFS, mOS, ORR, and DCR were 10.6 months, 15.8 months, 42.3%, and 88.6% of first-line anti-PD1/PDL1 and 3.0 months, 9.1 months, 11.6%, and 51.1% of second-line therapy or beyond, respectively. There were 80.6% and 34.0% of the patients suffering any-grade AEs and grade 3-4 AEs. Anti-PD1/PDL1 monotherapy might be considered as a safer alternative than combination regimens. Meanwhile, obvious toxicities in the first-line setting could not be neglected.
CONCLUSIONS
Anti-PD1/PDL1 showed encouraging efficacy and acceptable safety profile in aBTC and, thus, could be an alternative treatment.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Humans; Progression-Free Survival
PubMed: 35309350
DOI: 10.3389/fimmu.2022.801909 -
Medicine Mar 2023The triple combination of programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) inhibitors, radiotherapy (RT), and anti-angiogenesis agents has been widely... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The triple combination of programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) inhibitors, radiotherapy (RT), and anti-angiogenesis agents has been widely used in the treatment of solid tumors and has shown positive efficacy. We conducted a meta-analysis to evaluate the efficacy and safety of PD1/PDL1 inhibitors combined with anti-angiogenic agents and RT for the treatment of solid cancers.
METHODS
A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from inception to October 31, 2022. Studies involving patients with solid cancers who received PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents treatment that reported overall response rate, complete remission rate, disease control rate, and adverse events (AEs) were included. A random-effects or fixed-effects model was used for the pooled rates, and 95% confidence intervals (CIs) were determined for all outcomes. The quality of the included literature was assessed using the methodological index for nonrandomized studies critical appraisal checklist. Egger test was used to assess the publication bias in the included studies.
RESULTS
Ten studies (4 nonrandomized controlled trials and 6 single-arm trials), including 365 patients, were identified and included in the meta-analysis. The pooled overall response rate after treatment with PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents was 59% (95% CI: 48-70%), whereas the disease control rate and complete remission rate were 92% (95% CI: 81-103%) and 48% (95% CI: 35-61%), respectively. Moreover, the meta-analysis showed that compared with triple-regimen, monotherapy or dual-combination treatment did not improve overall survival (hazard ratio = 0.499, 95% CI: 0.399-0.734) and progression-free survival (hazard ratio = 0.522, 95% CI: 0.352-0.774). The pooled rate of grade 3 to 4 AEs was 26.9% (95% CI: 7.8%-45.9), and the common AEs to triple therapy included leukopenia (25%), thrombocytopenia (23.8%), fatigue (23.2%), gastrointestinal discomfort (22%), increased alanine aminotransferase (22%), and neutropenia (21.4%).
CONCLUSION
In the treatment of solid tumors, PD1/PDL1 inhibitors combined with RT and anti-angiogenic drugs achieved a positive response and better survival benefits than monotherapy or dual therapy. In addition, combination therapy is tolerable and safe.
REGISTRATION
PROSPERO ID: CRD42022371433.
Topics: Humans; Neoplasms; Angiogenesis Inhibitors; Immunotherapy
PubMed: 36897735
DOI: 10.1097/MD.0000000000033204 -
Evidence-based Complementary and... 2020Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers... (Review)
Review
Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects.
PubMed: 32454874
DOI: 10.1155/2020/9154738