scholarly journals Mesothelioma, a Review of Current Guidelines

Mesothelioma ◽  
2020 ◽  
Author(s):  
Sonia Maciá
Keyword(s):  
Poor Prognosis ◽  
Meta Analysis ◽  
Clinical Trial Data ◽  
Standard Of Care ◽  
Phase Iii ◽  
New Paradigm ◽  
Nccn Guidelines ◽  
Pivotal Study ◽  
Systemic Treatments ◽  
Current Guidelines

Mesothelioma is considered as a rare tumor originating in the mesothelial surfaces of pleura or, more rarely, in other sites such as peritoneum, which harbors a very poor prognosis. Despite clinical research efforts, lack of available therapies remains clear. Standard of care treatments and guidelines have not been evolved much along recent years. In this chapter, main guidelines will be reviewed, besides a systematic Pubmed review, with a focus on epidemiology, diagnosis tests, and approved local and systemic treatments, including most important advances. Searched terms included “mesothelioma,” “ESMO and NCCN guidelines,” “diagnosis,” “surgery,” “targeted therapy,” “clinical trials,” “palliative treatment,” and “meta-analysis.” First-line regimen recommendations have not evolved since the phase III pivotal study of cisplatin-pemetrexed was published, and this combination became the standard of care. Targeted therapies have brought disappointing results. However, recent clinical trial data with immunotherapies are bringing some light and may become a new paradigm in the following years.

scholarly journals A systematic review and network meta-analysis of adjuvant therapy for curatively resected biliary tract cancers

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
M. Kish ◽  
K. Chan ◽  
K. Perry ◽  
Y.J. Ko
Keyword(s):  
Systematic Review ◽  
Adjuvant Therapy ◽  
Biliary Tract ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Standard Of Care ◽  
Phase Iii ◽  
Quality Data ◽  
Qualitative Synthesis ◽  
Tract Cancer

Background Recent randomized controlled trials (rcts) have contributed high-quality data about adjuvant therapy in curatively resected biliary tract cancer (btc); however, a standard approach to treating those patients still has not been developed.Methods We conducted a systematic review of published studies and abstracts up to and including June 2018, choosing rcts involving patients with btc receiving adjuvant chemotherapy after complete surgical resection. Network meta-analysis methods were used for indirect comparisons of overall survival (os) and relapse-free survival (rfs) for various adjuvant therapies.Results Five rcts were included in qualitative synthesis, and three rcts (bilcap, prodige 12–accord 18, and bcat) had data sufficient for inclusion in the meta-analysis. Results from the indirect comparison demonstrated no significant improvement in os for capecitabine compared with gemcitabine or with gemcitabine–oxaliplatin (gemox), the hazard ratios (hrs) being 0.82 [95% confidence interval (ci): 0.53 to 1.27] and 0.86 (95% ci: 0.56 to 1.34) respectively. Similarly, no significant improvement in rfs was observed for capecitabine compared with gemcitabine or gemox.Conclusions Although in the present analysis, we found no statistically significant improvements in os or rfs for capecitabine compared with gemox or gemcitabine, capecitabine can—until further prospective trials are completed— be considered the standard of care in the adjuvant setting based on a single randomized phase iii study.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis

2017 ◽  
pp. 1-12
Author(s):  
Doah Cho ◽  
Felicia T. Roncolato ◽  
Johnathan Man ◽  
John Simes ◽  
Sarah J. Lord ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Predictors Of Success ◽  
Biologic Therapies ◽  
Therapeutic Success ◽  
Free Survival ◽  
Randomized Controlled ◽  
Phase Iii Trials

Purpose The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. Methods This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. Results Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively Conclusion Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.

Network Meta-analysis of Treatments for Chronic Plaque Psoriasis in Canada

2014 ◽  
Vol 18 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Aditya K. Gupta ◽  
Deanne Daigle ◽  
Danika C.A. Lyons
Keyword(s):  
Clinical Trials ◽  
Plaque Psoriasis ◽  
Meta Analysis ◽  
Severity Index ◽  
Phase Iii ◽  
Chronic Plaque Psoriasis ◽  
Phase Iii Clinical Trials ◽  
Statistical Framework ◽  
Consistency Model ◽  
Systemic Treatments

Background: Psoriasis affects approximately 500,000 Canadians. Eight treatments are currently licensed for chronic plaque psoriasis in Canada. Objective: To compare the efficacy of systemic treatments for chronic plaque psoriasis for the outcome > 75% reduction in the Psoriasis Area and Severity Index (PASI) using network meta-analysis. Methods: PubMed and clinicaltrials.gov databases were searched up until October 15, 2013, for phase III clinical trials. A consistency model based on a random-effects bayesian statistical framework was used to compare the rates of > 75% PASI reduction across trials. Results: Twenty-one studies were included in the network analysis. Infliximab had significantly greater odds of producing > 75% reduction in the PASI compared to all treatments. All treatments conferred greater odds of > 75% PASI reduction compared to placebo. Conclusion: Although infliximab had the highest efficacy relative to other systemic treatments for psoriasis, adverse effects, cost, and patient preferences should also be considered when deciding on treatment.

Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials

2017 ◽  
Vol 35 (6) ◽  
pp. 622-628 ◽  
Author(s):  
Richard Jackson ◽  
Eftychia-Eirini Psarelli ◽  
Sarah Berhane ◽  
Harun Khan ◽  
Philip Johnson
Keyword(s):  
Hepatocellular Carcinoma ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Hepatocellular Cancer ◽  
Standard Of Care ◽  
Exponential Model ◽  
Patient Data ◽  
Phase Iii ◽  
Disease Etiology ◽  
Hazard Ratios

Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log [hazard ratio], −0.27; 95% CI, −0.46 to −0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for “other” treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran’s Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients’ hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.

Pembrolizumab versus the standard of care for cancer therapy: A meta-analysis of 12 KEYNOTE trials comparing overall survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14159-e14159 ◽  
Author(s):  
Nathaniel Parker ◽  
Ammar Al-Obaidi ◽  
Quoc Van Truong ◽  
Robert Badgett
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Antineoplastic Agent ◽  
Standard Of Care ◽  
Phase Iii ◽  
Cancer Type ◽  
Random Effects Models ◽  
Phase Iii Trials

e14159 Background: Pembrolizumab (P) is an antineoplastic agent approved for multiple different tumor origins as well as tumor agnostic based on MSI status. Thus understanding the tumor characteristics most predictive of response is essential. Living meta-analysis provides a method to continuously assimilate emerging trials. In this study, we created a living meta-analysis to compare the effect of P on overall survival (OS). Methods: Meta-analysis was conducted according to the PRISMA guidelines. PubMed and Cochrane databases, and conference abstracts (e.g. ASCO, ESMO), were searched for phase III KEYNOTE RCT’s that reported OS among cancer patients receiving P. Results: 12 phase III trials involving 7,319 patients (3,861 in P arms) treated for 6 different types of cancer were retrieved. Median follow up was 12.9 months [range: 0.1-35.5]. Treatment was P alone, SOC chemo, and P + chemo in 11 (40%), 13 (46%), and 4 (14%) arms, respectively. P significantly improved OS (HR 0.71, 95% CI: 0.59-0.85, p <0.001, I2 = 0%) when used in any cancer type, setting, or therapy for advanced refractory or chemo-naïve cancer patients. The mean median OS was 12.5 vs 11.1 months in the total populations for all P and control arms, respectively (Table). Conclusions: Among all trials, P was associated with improved OS. Additional meta-analysis will be performed with R software (version 3.3.3; R Fdn.). Random-effects models will be used to compare OS. Heterogeneity will be assessed with Cochrane Q -statistic and quantified with I2test via subgroup analyses for cancer type, setting, therapy, and PD-L1%. This meta-analysis is continuously updated at http://openmetaanalysis.github.io/checkpoint-inhibitors. [Table: see text]

scholarly journals Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Iyad Alnahhas ◽  
Mouaz Alsawas ◽  
Appaji Rayi ◽  
Joshua D Palmer ◽  
Raju Raval ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Current Standard ◽  
Prospective Data ◽  
Free Survival ◽  
Mgmt Promoter ◽  
Newly Diagnosed Glioblastoma

Abstract Background The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT. Methods We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020. Results The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18–15.04) with a median PFS of 4.99 months (95% CI, 4.25–5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19–26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41–11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible. Conclusions This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.

scholarly journals Metastatic extramammary paget disease, a remarkable clinical case and a brief review of a rare disease

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Leonor Fernandes ◽  
Joana Graça ◽  
Leonor Vasconcelos de Matos ◽  
Rita Sampaio ◽  
Mafalda Miranda Baleiras ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Rare Disease ◽  
Poor Prognosis ◽  
Clinical Case ◽  
Standard Of Care ◽  
Primary Treatment ◽  
Metastatic Site ◽  
Paget Disease ◽  
The Central Nervous System ◽  
Current Guidelines

Extramammary Paget Disease (EMPD) is an often-misdiagnosed rare disorder, whose cause remains unknown. Diagnosis is confirmed by skin biopsy. Primary treatment for EMPD is surgery. Recurrence is common in the first two years and prognosis is good if the disease is localized and there is no underlying associated cancer. Patients with invasive and metastatic EMPD are uncommon and exhibit a poor prognosis, even when there is good response to a first chemotherapy line. Multiple chemotherapeutic regimens, with varying levels of success, have been attempted, but standard of care is not established. The central nervous system seems to be a common metastatic site with better survival than visceral metastasis.We report a case of metastatic EMPD that addresses the difficulties associated with the treatment of this rare disease, that has no current guidelines.

Citation Impact of Breakthrough Interventions for Malignant Blood Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3115-3115
Author(s):  
Benjamin Djulbegovic ◽  
Heloisa P. Soares ◽  
Ambuj Kumar
Keyword(s):  
Clinical Research ◽  
Hematological Malignancies ◽  
Citation Count ◽  
Citation Impact ◽  
Standard Of Care ◽  
Phase Iii ◽  
Blood Disorders ◽  
Nccn Guidelines ◽  
Scientific Attention ◽  
Highly Cited

Abstract Background: Citation count is a widely accepted measure of how much a study has drawn attention of other scientists and clinicians. The studies that have generated new, breakthrough interventions that potentially can affect the lives of many patients are expected to be widely disseminated. In this work, we test hypothesis if the breakthrough interventions as discovered in the NCI sponsored phase III hematological malignancies trials received high citation count. NCI trials account for almost 100% of publicly sponsored phase III trials in the US. Methods: We evaluated all randomized controlled trials (RCTs) that have been conducted by six NCI sponsored cooperative oncology groups (COGs). We included all trials that were completed by 2002. Here, we focus on hematological malignancies trials. We arbitrarily defined as “breakthrough interventions” those interventions that were judged by the investigators highly preferred so they should become standard of care and/or had an effect size was so large that their log hazard ratio for survival or event-free survival was −1 or less. The study which received more than 1,000 citations is considered as highly-cited clinical research paper. (Ioannidis JPA, JAMA 2005) Results: We evaluated 133 hematological-malignancy trials/comparisons. Ninety-two trials studied leukemias, 38 lymphomas and 3 either multiple myeloma or myelodysplastic syndrome. 26 (20%) interventions were found to meet the criteria for the “breaktrough interventions”. None of the papers met criteria for highly-cited research. Citation counts ranged from 4–311 (median: 62). The highest-cited paper reported the use of All-trans-retinoic acid for induction and maintanence of acute promyelocytic leukemia. This paper is currently cited in NCCN guidelines and the NCI PQD® treatment website. Conclusions: The best clinical research in hematological malignancies has received relatively little scientific attention. Elucidating the factors that could explain these findings may help identify the barriers that prevent generation and dissemination of evidence of vital importance for improving outcomes of patients with malignant blood disorders.

A meta-analysis of two randomized, double-blind, placebo-controlled, phase III studies in patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK/ZK to determine clinical benefit on progression-free survival (PFS) in high LDH pts

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3529-3529 ◽  
Author(s):  
P. Major ◽  
T. Trarbach ◽  
H. Lenz ◽  
D. Kerr ◽  
K. Pendergrass ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Antiangiogenic Therapy ◽  
Phase Iii ◽  
Bleeding Complications ◽  
Poor Performance Status ◽  
P Value ◽  
Baseline Serum

3529 Background: PTK/ZK is an oral, antiangiogenic inhibitor of tyrosine kinase signaling of all known vascular endothelial growth factor receptors (VEGFR). PTK/ZK in combination with FOLFOX4 has been investigated in first line (CONFIRM 1[C1]) and second line (CONFIRM 2 [C2]) mCRC pts. Methods: In both trials, pts were randomized to receive PTK/ZK or placebo. Since high LDH and poor performance status (PS) have been shown to indicate poor prognosis in mCRC, pts were stratified by baseline serum LDH (≤ or > 1.5 X ULN) and PS (0, 1–2), yielding 4 strata per trial. Exploratory analysis of the high LDH strata in C1 indicated that these pts may derive the most benefit from PTK/ZK treatment. The purpose of this pre-planned meta-analysis of C1 and C2 is to determine whether the treatment effect of C1 and C2 are consistent. Results: Both trials showed strikingly similar results. High LDH pts comprise approximately 30% of the total pt population. PTK/ZK seems to have the same strong effect on PFS in high LDH pts in both 1st and 2nd line mCRC with a HR for PFS of 0.67 (p =0.010) for C1 and 0.63 (p < 0.001) for C2 (N=250 and N=316, respectively). The safety profile of PTK/ZK was highly consistent. The most frequent grade 3/4 AEs attributable to PTK/ZK were hypertension, diarrhea, fatigue, nausea, vomiting and dizziness. Increases in AEs associated with antiangiogenic therapy such as bowel perforations and bleeding complications were not observed in the PTK/ZK arms of both trials. In the meta-analysis, PTK/ZK effect on PFS is moderate in the overall population (HR 0.85, p-value 0.005). In contrast, the effect on PFS is strong and clinically meaningful in the high LDH population (HR 0.65, p-value < 0.001, N=566). Conclusion: This meta-analysis is the largest study of poor prognosis pts with high serum LDH in metastatic colorectal cancer. These data suggest that PTK/ZK significantly improves PFS in high LDH pts. Further evaluation of PTK/ZK in this pt population is planned. [Table: see text]

Adult participation in oncology clinical trials by indication, race, and age.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17586-e17586
Author(s):  
Austin James Combest ◽  
Dirk J. Reitsma ◽  
Angelena Moseley ◽  
Savanna D. Steele ◽  
Marie-Edith Anne Bonneterre
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Ethnic Diversity ◽  
Age Groups ◽  
Standard Of Care ◽  
The United States ◽  
Phase Iii ◽  
Trial Participation ◽  
Clinical Trial Participation ◽  
Nccn Guidelines

e17586 Background: According to the National Cancer Institute (NCI), approximately 3 percent of adult cancer patients participate in clinical trials despite the NCCN guidelines frequently recommending clinical trials as standard of care in many circumstances (Mooney, 2010). In a large analysis of NCI Cancer Therapy Evaluation Program (CTEP) trials, 40 percent of trials failed to achieve minimum enrollment, including 3 of 5 phase III trials (Cheng, 2010). Additionally, concerns about unequal access to clinical trials led Congress to enact the National Institutes of Health (NIH) Revitalization Act 20 years ago (June 10, 1993). Using data from Ipsos’ Tandem Oncology Monitor, a robust, nationwide system that collects actual prescriptions and clinical trial participation by indication from 500 oncologists and hematologists from the United States, we evaluated current participation and ethnic diversity in clinical trials. Methods: We assessed adult clinical trial participation from October 2011 to September 2012. Age, ethnicity and practice type were also collected to identify descriptive trends. Results: With regards to indication, clinical trial participation ranged from 1 percent (prostate, renal cell and head and neck) to 12 percent (thyroid) averaging between 2 and 3 percent. We observed a decline in first-line metastatic melanoma participation between pre- and post- vemurafenib/ipilimumab approval (9%-pre versus 2%-post). Patient diversity results are included in the Table. Conclusions: Despite efforts to increase oncology clinical trial participation, we have observed overall low clinical trial participation. Additionally, we observed better trial participation in the youngest age groups and minor differences between ethnic categories. Continued focus on increasing trial participation and patient diversity is still needed. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document