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The Cochrane Database of Systematic... Sep 2015Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biologics. Although there is consensus that these therapies reduce the frequency of relapses, their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials.
OBJECTIVES
To compare the benefit and acceptability of interferon beta-1b, interferon beta-1a (Avonex, Rebif), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine and immunoglobulins for the treatment of people with RRMS and to provide a ranking of these treatments according to their benefit and acceptability, defined as the proportion of participants who withdrew due to any adverse event.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, which contains trials from CENTRAL (2014, Issue 9), MEDLINE (1966 to 2014), EMBASE (1974 to 2014), CINAHL (1981 to 2014), LILACS (1982 to 2014), clinicaltrials.gov and the WHO trials registry, and US Food and Drug Administration (FDA) reports. We ran the most recent search in September 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that studied one or more of the 15 treatments as monotherapy, compared to placebo or to another active agent, for use in adults with RRMS.
DATA COLLECTION AND ANALYSIS
Two authors independently identified studies from the search results and performed data extraction. We performed data synthesis by pairwise meta-analysis and network meta-analysis. We assessed the quality of the body of evidence for outcomes within the network meta-analysis according to GRADE, as very low, low, moderate or high.
MAIN RESULTS
We included 39 studies in this review, in which 25,113 participants were randomised. The majority of the included trials were short-term studies, with a median duration of 24 months. Twenty-four (60%) were placebo-controlled and 15 (40%) were head-to-head studies.Network meta-analysis showed that, in terms of a protective effect against the recurrence of relapses in RRMS during the first 24 months of treatment, alemtuzumab, mitoxantrone, natalizumab, and fingolimod outperformed other drugs. The most effective drug was alemtuzumab (risk ratio (RR) versus placebo 0.46, 95% confidence interval (CI) 0.38 to 0.55; surface under the cumulative ranking curve (SUCRA) 96%; moderate quality evidence), followed by mitoxantrone (RR 0.47, 95% CI 0.27 to 0.81; SUCRA 92%; very low quality evidence), natalizumab (RR 0.56, 95% CI 0.47 to 0.66; SUCRA 88%; high quality evidence), and fingolimod (RR 0.72, 95% CI 0.64 to 0.81; SUCRA 71%; moderate quality evidence).Disability worsening was based on a surrogate marker, defined as irreversible worsening confirmed at three-month follow-up, measured during the first 24 months in the majority of included studies. Both direct and indirect comparisons revealed that the most effective treatments were mitoxantrone (RR versus placebo 0.20, 95% CI 0.05 to 0.84; SUCRA 96%; low quality evidence), alemtuzumab (RR 0.35, 95% CI 0.26 to 0.48; SUCRA 94%; low quality evidence), and natalizumab (RR 0.64, 95% CI 0.49 to 0.85; SUCRA 74%; moderate quality evidence).Almost all of the agents included in this review were associated with a higher proportion of participants who withdrew due to any adverse event compared to placebo. Based on the network meta-analysis methodology, the corresponding RR estimates versus placebo over the first 24 months of follow-up were: mitoxantrone 9.92 (95% CI 0.54 to 168.84), fingolimod 1.69 (95% CI 1.32 to 2.17), natalizumab 1.53 (95% CI 0.93 to 2.53), and alemtuzumab 0.72 (95% CI 0.32 to 1.61).Information on serious adverse events (SAEs) was scanty, characterised by heterogeneous results and based on a very low number of events observed during the short-term duration of the trials included in this review.
AUTHORS' CONCLUSIONS
Conservative interpretation of these results is warranted, since most of the included treatments have been evaluated in few trials. The GRADE approach recommends providing implications for practice based on moderate to high quality evidence. Our review shows that alemtuzumab, natalizumab, and fingolimod are the best choices for preventing clinical relapses in people with RRMS, but this evidence is limited to the first 24 months of follow-up. For the prevention of disability worsening in the short term (24 months), only natalizumab shows a beneficial effect on the basis of moderate quality evidence (all of the other estimates were based on low to very low quality evidence). Currently, therefore, insufficient evidence is available to evaluate treatments for the prevention of irreversible disability worsening.There are two additional major concerns that have to be considered. First, the benefit of all of these treatments beyond two years is uncertain and this is a relevant issue for a disease with a duration of 30 to 40 years. Second, short-term trials provide scanty and poorly reported safety data and do not provide useful evidence in order to obtain a reliable risk profile of treatments. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary also to evaluate non-randomised studies and post-marketing reports released from the regulatory agencies. Finally, more than 70% of the studies included in this review were sponsored by pharmaceutical companies and this may have influenced the results.There are three needs that the research agenda should address. First, randomised trials of direct comparisons between active agents would be useful, avoiding further placebo-controlled studies. Second, follow-up of the original trial cohorts should be mandatory. Third, more studies are needed to assess the medium and long-term benefit and safety of immunotherapies and the comparative safety of different agents.
Topics: Adult; Humans; Immunologic Factors; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 26384035
DOI: 10.1002/14651858.CD011381.pub2 -
Biomedicines Aug 2021In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs)... (Review)
Review
Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel ( = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe.
PubMed: 34440246
DOI: 10.3390/biomedicines9081042 -
The Cochrane Database of Systematic... May 2016Malignant pleural effusion (MPE) is a common problem for people with cancer as a result of malignant infiltration of the pleura. It is usually associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malignant pleural effusion (MPE) is a common problem for people with cancer as a result of malignant infiltration of the pleura. It is usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid including administration of a pleurodesis agent (either via a chest tube or at thoracoscopy) or indwelling pleural catheter insertion.
OBJECTIVES
To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success. Additionally, to quantify differences in patient-reported outcomes and adverse effects between management strategies.
SEARCH METHODS
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE; EBSCO CINAHL; SCI-EXPANDED and SSCI (ISI Web of Science) to April 2015.
SELECTION CRITERIA
We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data on study design, study characteristics, outcome measures, potential effect modifiers and risk of bias.The primary outcome measure was pleurodesis failure rate. Secondary outcome measures were adverse effects and complications, patient-reported control of breathlessness, quality of life, cost, mortality, duration of inpatient stay and patient acceptability.We performed network meta-analysis with random effects to analyse the primary outcome data and those secondary outcomes with enough data. We also performed pair-wise random-effects meta-analyses of direct comparison data. If interventions were not deemed jointly randomisable, or insufficient data were available, we reported the results by narrative synthesis. We performed sensitivity analyses to explore heterogeneity and to evaluate only those pleurodesis agents administered via a chest tube at the bedside.
MAIN RESULTS
Of the 1888 records identified, 62 randomised trials, including a total of 3428 patients, were eligible for inclusion. All studies were at high or uncertain risk of bias for at least one domain.Network meta-analysis evaluating the rate of pleurodesis failure, suggested talc poudrage to be a highly effective method (ranked second of 16 (95% credible interval (Cr-I) 1 to 5)) and provided evidence that it resulted in fewer pleurodesis failures than eight other methods. The estimated ranks of other commonly used agents were: talc slurry (fourth; 95% Cr-I 2 to 8), mepacrine (fourth; 95% Cr-I 1 to 10), iodine (fifth; 95% Cr-I 1 to 12), bleomycin (eighth; 95% Cr-I 5 to 11) and doxycyline (tenth; 95% Cr-I 4 to 15). The estimates were imprecise as evidenced by the wide credible intervals and both high statistical and clinical heterogeneity.Most of the secondary outcomes, including adverse events, were inconsistently reported by the included studies and the methods used to describe them varied widely. Hence the majority of the secondary outcomes were reported descriptively in this review. We obtained sufficient data to perform network meta-analysis for the most commonly reported adverse events: pain, fever and mortality. The fever network was imprecise and showed substantial heterogeneity, but suggested placebo caused the least fever (ranked first of 11 (95% Cr-I 1 to 7)) and mepacrine and Corynebacterium parvum (C. parvum) appeared to be associated with the most fever (ranked tenth (95% Cr-I 6 to 11) and eleventh (95% Cr-I 7 to 11) respectively). No differences between interventions were revealed by the network meta-analysis of the pain data. The only potential difference in mortality identified in the mortality network was that those receiving tetracycline appeared to have a longer survival than those receiving mitoxantrone (OR 0.16 (95% Confidence Interval (CI) 0.03 to 0.72)). Indwelling pleural catheters were examined in two randomised studies, both of which reported improved breathlessness when compared to talc slurry pleurodesis, despite lower pleurodesis success rates.The risk of bias in a number of the included studies was substantial, for example the vast majority of studies were unblinded, and the methods used for sequence generation and allocation concealment were often unclear. Overall, however, the risk of bias for all studies was moderate. We have not reported the GRADE quality of evidence for the outcomes, as the role of GRADE is not well established in the context of Network Meta-analysis (NMA).
AUTHORS' CONCLUSIONS
Based on the available evidence, talc poudrage is a more effective pleurodesis method in MPE than a number of other frequently used methods, including tetracycline and bleomycin. However further data are required to definitively confirm whether it is more effective than certain other commonly used interventions such as talc slurry and doxycycline, particularly in view of the high statistical and clinical heterogeneity within the network and the high risk of bias of many of the included studies. Based on the strength of the evidence from both direct and indirect comparisons of randomised data of sclerosants administered at the bedside, there is no evidence to suggest large differences between the other highly effective methods (talc slurry, mepacrine, iodine and C. parvum). However, local availability, global experience of these agents and their adverse events, which may not be identified in randomised trials, must also be considered when selecting a sclerosant. Further research is required to delineate the roles of different treatments according to patient characteristics (e.g. according to their prognosis or presence of trapped lung) and to explore patient-centred outcomes, such as breathlessness and quality of life, in more detail. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.
Topics: Adult; Bleomycin; Doxycycline; Fever; Humans; Iodine; Pleural Effusion, Malignant; Pleurodesis; Quinacrine; Randomized Controlled Trials as Topic; Talc; Treatment Failure
PubMed: 27155783
DOI: 10.1002/14651858.CD010529.pub2 -
Journal of Clinical Oncology : Official... Oct 2014To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). (Review)
Review
PURPOSE
To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC).
METHODS
The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature.
RESULTS
When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ((223)Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib.
RECOMMENDATIONS
Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or (223)Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or combinations of therapies. Palliative care should be offered to all patients.
Topics: Abiraterone Acetate; Androstadienes; Benzamides; Docetaxel; Humans; Male; Neoplasm Metastasis; Nitriles; Phenylthiohydantoin; Practice Guidelines as Topic; Prednisone; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Randomized Controlled Trials as Topic; Taxoids
PubMed: 25199761
DOI: 10.1200/JCO.2013.54.8404 -
PloS One 2018Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer...
BACKGROUND
Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias.
METHODS
A systematic literature search was performed in the databases PubMed, CINAHL Complete, the Cochrane Library and Web of Science Core Collection for costs-effectiveness analyses, model-based economic evaluations, cost-of-illness analyses and budget impact analyses. Reported costs were inflated to 2015 US$ purchasing power parities. Quality assessment and risk of bias assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist and the Bias in Economic Evaluations checklist, respectively.
RESULTS
In total, 38 articles were identified by the systematic literature search. The methodological quality of the included studies varied widely, and there was considerable risk of bias. The cost-effectiveness treatments for CRPC and mCRPC was assessed with incremental cost-effectiveness ratios ranging from dominance for mitoxantrone to $562,328 per quality-adjusted life year gained for sipuleucel-T compared with prednisone alone. Annual costs for the treatment of castration-resistant prostate cancer ranged from $3,067 to $77,725.
CONCLUSION
The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality-adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations. High-quality cost-effectiveness analyses based on randomized controlled trials are needed in order to make informed decisions on the management of castration-resistant prostate cancer and the resulting financial impact on the healthcare system.
Topics: Aged; Antineoplastic Agents; Bias; Cost-Benefit Analysis; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms, Castration-Resistant; Quality-Adjusted Life Years; Tissue Extracts
PubMed: 30517165
DOI: 10.1371/journal.pone.0208063 -
Human Vaccines & Immunotherapeutics 2015Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects... (Review)
Review
Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders.
Topics: Autoimmune Diseases; Child; Chorea; Cyclophosphamide; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Immunotherapy; Methylprednisolone; Mitoxantrone; Multiple Sclerosis; Natalizumab; Nervous System; Neurodegenerative Diseases; Neuromyelitis Optica; Obsessive-Compulsive Disorder; Plasma Exchange; Rituximab; Streptococcal Infections; Tourette Syndrome
PubMed: 26266339
DOI: 10.1080/21645515.2015.1061161 -
The Cochrane Database of Systematic... Apr 2017The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions.
OBJECTIVES
1. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;2. to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;3. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for treatment started after a first attack ('early treatment') compared with treatment started after a second attack or at another later time point ('delayed treatment').
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS, clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration (FDA) reports, and searched for unpublished studies (until December 2016).
SELECTION CRITERIA
We included randomised and observational studies that evaluated one or more drugs as monotherapy in adult participants with a first clinical attack suggestive of MS. We considered evidence on alemtuzumab, azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif®, Avonex®), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated interferon beta-1a, rituximab and teriflunomide.
DATA COLLECTION AND ANALYSIS
Two teams of three authors each independently selected studies and extracted data. The primary outcomes were disability-worsening, relapses, occurrence of at least one serious adverse event (AE) and withdrawing from the study or discontinuing the drug because of AEs. Time to conversion to clinically definite MS (CDMS) defined by Poser diagnostic criteria, and probability to discontinue the treatment or dropout for any reason were recorded as secondary outcomes. We synthesized study data using random-effects meta-analyses and performed indirect comparisons between drugs. We calculated odds ratios (OR) and hazard ratios (HR) along with relative 95% confidence intervals (CI) for all outcomes. We estimated the absolute effects only for primary outcomes. We evaluated the credibility of the evidence using the GRADE system.
MAIN RESULTS
We included 10 randomised trials, eight open-label extension studies (OLEs) and four cohort studies published between 2010 and 2016. The overall risk of bias was high and the reporting of AEs was scarce. The quality of the evidence associated with the results ranges from low to very low. Early treatment versus placebo during the first 24 months' follow-upThere was a small, non-significant advantage of early treatment compared with placebo in disability-worsening (6.4% fewer (13.9 fewer to 3 more) participants with disability-worsening with interferon beta-1a (Rebif®) or teriflunomide) and in relapses (10% fewer (20.3 fewer to 2.8 more) participants with relapses with teriflunomide). Early treatment was associated with 1.6% fewer participants with at least one serious AE (3 fewer to 0.2 more). Participants on early treatment were on average 4.6% times (0.3 fewer to 15.4 more) more likely to withdraw from the study due to AEs. This result was mostly driven by studies on interferon beta 1-b, glatiramer acetate and cladribine that were associated with significantly more withdrawals for AEs. Early treatment decreased the hazard of conversion to CDMS (HR 0.53, 95% CI 0.47 to 0.60). Comparing active interventions during the first 24 months' follow-upIndirect comparison of interferon beta-1a (Rebif®) with teriflunomide did not show any difference on reducing disability-worsening (OR 0.84, 95% CI 0.43 to 1.66). We found no differences between the included drugs with respect to the hazard of conversion to CDMS. Interferon beta-1a (Rebif®) and teriflunomide were associated with fewer dropouts because of AEs compared with interferon beta-1b, cladribine and glatiramer acetate (ORs range between 0.03 and 0.29, with substantial uncertainty). Early versus delayed treatmentWe did not find evidence of differences between early and delayed treatments for disability-worsening at a maximum of five years' follow-up (3% fewer participants with early treatment (15 fewer to 11.1 more)). There was important variability across interventions; early treatment with interferon beta-1b considerably reduced the odds of participants with disability-worsening during three and five years' follow-up (OR 0.52, 95% CI 0.32 to 0.84 and OR 0.57, 95% CI 0.36 to 0.89). The early treatment group had 19.6% fewer participants with relapses (26.7 fewer to 12.7 fewer) compared to late treatment at a maximum of five years' follow-up and early treatment decreased the hazard of conversion to CDMS at any follow-up up to 10 years (i.e. over five years' follow-up HR 0.62, 95% CI 0.53 to 0.73). We did not draw any conclusions on long-term serious AEs or discontinuation due to AEs because of inadequacies in the available data both in the included OLEs and cohort studies.
AUTHORS' CONCLUSIONS
Very low-quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses. The advantage of early treatment compared with delayed on disability-worsening was heterogeneous depending on the actual drug used and based on very low-quality evidence. Low-quality evidence suggests that the chances of relapse are less with early treatment compared with delayed. Early treatment reduced the hazard of conversion to CDMS compared either with placebo, no treatment or delayed treatment, both in short- and long-term follow-up. Low-quality evidence suggests that early treatment is associated with fewer participants with at least one serious AE compared with placebo. Very low-quality evidence suggests that, compared with placebo, early treatment leads to more withdrawals or treatment discontinuation due to AEs. Difference between drugs on short-term benefit and safety was uncertain because few studies and only indirect comparisons were available. Long-term safety of early treatment is uncertain because of inadequately reported or unavailable data.
Topics: Adjuvants, Immunologic; Cladribine; Cohort Studies; Crotonates; Disease Progression; Glatiramer Acetate; Humans; Hydroxybutyrates; Immunosuppressive Agents; Interferon beta-1a; Multiple Sclerosis; Nitriles; Publication Bias; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Toluidines
PubMed: 28440858
DOI: 10.1002/14651858.CD012200.pub2 -
Journal of Clinical Oncology : Official... Feb 2019Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist... (Meta-Analysis)
Meta-Analysis
PURPOSE
Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen.
METHODS
Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases).
RESULTS
Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001).
CONCLUSION
When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.
Topics: Antineoplastic Combined Chemotherapy Protocols; Black People; Clinical Trials, Phase III as Topic; Docetaxel; Humans; Male; Mitoxantrone; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; White People
PubMed: 30576268
DOI: 10.1200/JCO.18.01279