Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review.
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ABSTRACT:
SUBMITTER: Indini A
PROVIDER: S-EPMC7961496 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite advances in the treatment of many pediatric solid tumors, children with aggressive and high-risk disease continue to have a dismal prognosis. For those presenting with metastatic or recurrent disease, multiple rounds of intensified chemotherapy and radiation are the typical course of action, but more often than not, this fails to control the progression of the disease. Thus, new therapeutics are desperately needed to improve the outcomes for these children. Recent advances in our understanding of both the immune system's biology and its interaction with tumors have led to the development of novel immunotherapeutics as alternative treatment options for these aggressive malignancies. Immunotherapeutic approaches have shown promising results for pediatric solid tumors in early clinical trials, but challenges remain concerning safety and anti-tumor efficacy. In this review, we aim to discuss and summarize the main classes of immunotherapeutics used to treat pediatric solid tumors.
| S-EPMC6966467 | biostudies-literature
Project description:Immunotherapy has evolved considerably in the last decade and is becoming an integral component of the armamentarium for the treatment of patients with advanced solid tumors. It is important for clinicians, especially surgeons, to understand the basic principles of novel immunotherapies and the immune system. This review summarizes the evolution of the most relevant immunotherapies, their mechanisms of action, the data supporting their clinical use, and integration of immunotherapy into multidisciplinary management of solid tumors. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of immunotherapy.
| S-EPMC4044916 | biostudies-other
Project description:With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel-novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of trials of novel-novel combination therapies involving immunotherapies or molecular targeted therapies in advanced solid tumors. A MEDLINE search was conducted using a modified Cochrane Highly Sensitive Search Strategy for published clinical trials between July 1, 2017, and June 30, 2020, in the top-ranked medical and oncology journals. Trials were evaluated according to a criterion adapted from previously published Food and Drug Administration guidance and other key considerations in designing trials of combinations. This included the presence of a strong biological rationale, the use of a new established or emerging predictive biomarker prospectively incorporated into the clinical trial design, appropriate comparator arms of monotherapy or supportive external data sources and a primary endpoint demonstrating a clinically meaningful benefit. Of 32 identified trials, there were 11 (34%) trials of the novel-novel combination of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy, and 10 (31%) trials of anti-PD-1/PD-L1 and anti-vascular endothelial growth factor (VEGF) combination therapy. 20 (62.5%) trials were phase II trials, while 12 (37.5%) were phase III trials. Most (72%) trials lacked significant preclinical evidence supporting the development of the combination in the given indication. A majority of trials (69%) were conducted in biomarker unselected populations or used pre-existing biomarkers within the given indication for patient selection. Most studies (66%) were considered to have appropriate comparator arms or had supportive external data sources such as prior studies of monotherapy. All studies were evaluated as selecting a clinically meaningful primary endpoint. In conclusion, designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design. Designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design.
| S-EPMC8256733 | biostudies-literature
Project description:PurposeTo evaluate the effect of Bevacizumab in combination with chemotherapy on overall survival of patients with metastatic solid tumors.DesignA systematic literature search to identify randomized trials comparing chemotherapy with and without Bevacizumab in metastatic cancer. The primary end point was overall survival (OS) and the secondary end points were progression free survival (PFS) and toxicity. A meta-analysis was performed for each tumor type and for the combination of all tumors.Results24 randomized trials with 8 different types of malignancies were included in this meta-analysis. Patients treated with Bevacizumab had an OS benefit, hazard ratio (HR) 0.89 (95% CI 0.84-0.93, P<0.00001 I(2)-4%). The combined analysis showed a PFS benefit with a HR 0.71 (95% CI 0.68-0.74, P<0.00001, I(2)-54%). The toxicity analysis showed a statistically significant increase in fatal adverse events (FAEs) in the Bevacizumab treatment arm, risk ratio (RR) 1.47 (95% CI 1.1-1.98). A separate analysis of the lung cancer trials showed an increased risk of fatal pulmonary hemorrhage with a RR of 5.65 (95% CI 1.26-25.26). The risk of G3-4 adverse events was increased: RR 1.2 (95% CI 1.15-1.24).Conclusionin this combined analysis Bevacizumab improved OS (with little heterogeneity) and PFS. These results should be considered in the light of lack of markers predictive of response and the increased severe and fatal toxicity seen with Bevacizumab treatment.
| S-EPMC3551962 | biostudies-literature
Project description:Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet. Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included. Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of "ICI-favoring" gut microbiome (P = 0.0476). Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.
| S-EPMC8012896 | biostudies-literature
Project description:Background: Using progression-free survival (PFS)2, time from randomization to 2nd disease progression or death, is proposed as a surrogate for overall survival (OS) in oncology clinical trials. We used published data from solid tumor trials to assess whether PFS2 and OS are correlated. Methods: A literature search identified studies that reported PFS, PFS2, and OS. Two reviewers screened for eligibility, and documented PFS2, PFS or time from 1st to 2nd disease progression or death and OS. Correlation between PFS2 and OS was assessed using: (1) Kendall's Tau + Pearson's correlation coefficient in randomized controlled trials (RCTs); (2) Meta-analysis with the random effects model to compute the pooled correlation of PFS2 and OS. Results: Overall, 133 studies met search criteria, 15 (28 arms) had complete PFS2 and OS data in ovarian, gastric, colorectal, prostate, lung, renal and breast cancers. A positive correlation for PFS2 and OS was found for all 15 studies (Kendall's Tau = 0.7 [95% CIs 0.54, 0.78]); 10 RCTs (Pearson's correlation coefficient = 0.86); and meta-analysis from 7 trials (pooled Spearman's correlation coefficient = 0.84 [p = 0.0001; 95% CIs 0.71, 0.96]). Conclusions: In this retrospective analysis PFS2 strongly correlates with OS supporting the use of PFS2 to measure long-term clinical benefit when OS cannot be assessed.
| S-EPMC7456898 | biostudies-literature
Project description:Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan–Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09–3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27–3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.
| S-EPMC9696773 | biostudies-literature
Project description:Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes - neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN-upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0-1 with a median age at ICB treatment of 77 (range, 70-93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7-24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6-not reached] compared to 11.2 months [95% CI, 8.41-22.2] and 4.7 months [95% CI, 2.2-11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2-18.1] in the good LIPI group, 7.2 months [95% CI, 5.4-13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3-8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (<0.001). Poor LIPI score was associated with a poorer outcome in older patients treated with anti PD-(L)1. LIPI is a simple and accessible worldwide tool that can serve as a prognostic factor and can be useful for stratification benefit from ICB.
| S-EPMC9600023 | biostudies-literature
Project description:Substantial progress has been made in the treatment of pediatric solid tumors over the past 4 decades. However, children with metastatic and or recurrent disease continue to do poorly despite the aggressive multi-modality conventional therapies. The increasing understanding of the tumor biology and the interaction between the tumor and the immune system over the recent years have led to the development of novel immune-based therapies as alternative options for some of these high-risk malignancies. The safety and anti-tumor efficacy of various tumor vaccines and tumor-antigen specific immune cells are currently being investigated for various solid tumors. In early clinical trials, most of these cellular therapies have been well tolerated and have shown promising clinical responses. Although substantial work is being done in this field, the available knowledge for pediatric tumors remains limited. We review the contemporary early phase cell-based immunotherapy efforts for pediatric solid tumors and discuss the rationale and the challenges thereof.
| S-EPMC4629832 | biostudies-literature
Project description:Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting.
| S-EPMC4839383 | biostudies-literature