Citations

6596 Background: Several previous systematic reviews and meta-analyses have attempted to summarize toxicity of Immune checkpoint inhibitors (ICIs). However, very soon after each one of these reviews has been published, it became outdated. ICIs are currently used in 14 different cancers and data is rapidly evolving from new clinical trials. A living Systematic review, which is defined as a systematic review that is continually updated to incorporate relevant new evidence as it becomes available, is necessary in this situations. Therefore, we performed an updated systematic review and a meta-analysis which will serve as a foundation of a living Systematic review. Methods: MEDLINE, EMBASE and Cochrane were searched to identify phase 2 and 3 RCTs of PD-1/PD-L1 ICIs. Included studies compared either immunotherapy alone or combination with existing standard of care treatment and reported data for AE’s of interest. DerSimonian-Laird random effects Meta-Analysis was performed to derive pooled odds Ratio (OR) estimates for AE’s of interest. An infrastructure of a living systematic review is being developed and it includes monthly literature searches, cumulative meta-analysis and an online reporting platform. Results: We screened 6746 studies and 31 phase 3 and 2 phase 2 RCTs (n = 21,421) were included in the analysis. 22 RCTs used PD-1/PD-L1 ICIs as a single agent and 11 as a combination therapy. Selected toxicity estimates are summarized in a table. Conclusions: The meta-analysis updates previously published toxicity estimates and provides additional information about the risk of toxicities in single versus combination regimens. We have initiated the first living systematic review in oncology that will be continuously updated, incorporating relevant new evidence as it becomes available, and will provide accurate and up to date toxicity estimates to support clinical decision making. [Table: see text]

3524 Background: In mCRC, induction combination chemotherapy with targeted agents is considered the mainstay of treatment. This is typically followed by maintenance therapy vs. observation which had been examined in various trials. However, it remains unclear how best optimize maintenance strategy. We aim to evaluate comparative effectiveness to support best maintenance strategy. Methods: We searched PubMed, Embase, and Cochrane CENTRAL for randomized controlled trials (RCT) evaluating different maintenance strategies in previously untreated mCRC patients (pts): observation (obs), bevacizumab (bev), fluoropyrimidine (FP), FP+bev, or continuing induction regimen (CTX). Outcomes of interest included OS and PFS. The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White’s multivariate meta-regression to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Results: Twelve trials at low risk of bias (5540 pts) were included. Network meta-analysis shows no benefit of CTX over obs in terms of PFS (HR 0.7; 95% CI 0.46-1.09) and OS (HR 0.95; 95% CI 0.85-1.07). Compared to obs, maintenance therapy shows PFS benefit (HR 0.58; 95% CI 0.43-0.77) with only a trend in OS (HR 0.91; 95% CI 0.83-1.009). All maintenance strategies (FP, FP+bev, and bev) show significant improvement in PFS over obs. On SUCRA analysis, maintenance treatment (FP or FP+bev) has the highest likelihood of achieving better PFS (67.1% for FP and 99.8% for FP+bev) and OS (81.3% for FP and 73.2% for FP+bev). Conclusions: A maintenance strategy with at least a FP with or without the addition of bevacizumab is preferred. However, given the lack of a clear OS benefit, obs is an acceptable alternative. Optimal maintenance strategies should be dependent on factors including patient preferences, cost and toxicities. [Table: see text]

e13096 Background: Several studies have reported the association between atrial fibrillation (AF) and malignant cancer. Recently, results from a large cohort within the Women’s Health Study showed increased incident risk of breast, colon and lung cancer in patients with AF. Therefore, we performed a systematic review to assess the available evidence and a meta-analysis to define the strength of this association. Methods: MEDLINE, Cochrane and Scopus databases were searched for all prospective studies that reported the association between AF and presence of cancer. The HR for incident risk of common cancers was recorded (Breast, Lung, Colorectal) in patients with and without AF. Lung cancer was excluded because the data required for the analysis was not consistently reported. The DerSimonian-Laird random effects meta-analysis was performed to derive pooled Hazard Ratio (HR) estimates for incident risk of colorectal and breast cancer in patients with AF. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to expresses the percentage of the total observed variability due to study heterogeneity. Results: A total of 390,479 participants in 3 prospective studies were included in the analysis. Mean age of participants was 66.3 ± 6.5 with mean follow up for 12.6 years. Patients with atrial fibrillation had 27% more risk of developing colorectal cancer [HR 1.27 (1.07-1.51) p < 0.005, I2= 73%] and 14% more risk of developing breast cancer [HR 1.14 (1.03-1.26) p = 0.01, I2= 37%] as compared to those without atrial fibrillation. Applying these hazard ratios to age adjusted yearly incidence ratios from 2000-2015, one in 5824 new onset AF cases will develop CRC and one in 7474 new onset AF cases will develop breast cancer. Conclusions: There is small but statistically significant increase in risk of subsequent diagnosis of colorectal or breast cancer diagnosis in patients with AF. Shared risk factors such as old age or systemic disease processes may explain this association. While the results of this analysis raise interesting questions for future search, these results should not be used as basis to initiate cancer screening for an occult cancer in a patient with AF.

e12057 Background: Several RCTs have evaluated a shorter duration of T ( < 12 months) with hopes of similar efficacy, reduced cardiotoxicity, cost and burden of treatment. Of the 5 major studies, PERSPHONE showed that 6 months was non-inferior compared to 12 months. However, four additional studies of shorter duration failed to demonstrate non-inferiority. Therefore, we performed an updated systematic review and a meta-analysis to assess the optimal duration of adjuvant T. Methods: MEDLINE, EMBASE, Cochrane, Scopus and conference proceedings were searched to identify RCTs comparing one year of adjuvant T with a shorter duration in early-stage HER2+ breast cancer. The DerSimonian-Laird random-effects Meta-Analysis was performed using CMAv3 software to derive pooled Hazard Ratio (HR) estimates for overall survival (OS, Disease-Free Survival (DFS) and Odds Ratio(OR) estimates of cardiac toxicity. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. The risk for bias was assessed using the Cochrane Collaboration’s tool. Results: We screened 1772 citations and identified 5 studies(n = 11,377) for analysis. 5691 patients were randomized to 12 months of adjuvant T while 5686 were randomized to a shorter duration (3 studies evaluated 6 vs 12 months, 2 studies evaluated 9 weeks vs 12 months). OS (HR, 1.16, 95% CI 1.03-1.31, P= 0.015,I2 0.00, p= 0.837) and DFS (HR, 1.14, 95% CI 1.02-1.26 , P = 0.016,I2 14.90, p= 0.319) were significantly worse in patients receiving shorter duration T as compared to 12 months. Cardiotoxicity was significantly higher in the 12 month group vs shorter duration (OR, 2.10, 95% CI 1.58-2.80, p = 0.000 ,I2 51.182, p= 0.085). Grade 3/4 cardiac events and cardiac events leading to discontinuation of therapy were significantly higher in patients receiving 12 months (HR 2.06, 95% CI 1.60-2.63, P = 0.000, I2 3.967, p= 0.384). There was no significant heterogeneity among studies. Risk of bias was low. Conclusions: Twelve months of adjuvant T is associated with significantly better DFS and OS compared to a shorter duration. As such, 12 months should remain the standard of care for most patients. There is an unmet need to identify lower risk groups which might do well with from shorter duration of HER2-directed therapy.

Introduction Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, usually caused by tobacco smoking, but other important risk factors include exposures to combustion products of biomass fuels and environmental pollution. The introduction of several new (combination) inhaler therapies, increasing uncertainty about the role of inhaled corticosteroids and a rapid proliferation of the literature on management of stable COPD in general, call for novel ways of evidence synthesis in this area. A systematic review and evidence map can provide the basis for shared decision-making tools and help to establish a future research agenda. Methods and analysis This systematic review will follow an umbrella systematic review design (also called overview of reviews). We plan to conduct a comprehensive literature search of Ovid MEDLINE (including epub ahead of print, in process and other non-indexed citations), Ovid Embase, Ovid Cochrane Database of Systematic Reviews and Scopus from database inception to the present. We will include systematic reviews that assessed the effectiveness of any pharmacological or non-pharmacological intervention on one or more patient-important outcomes and/or lung function in patients with stable COPD. For every intervention/outcome pair, one systematic review will be included. An a priori protocol will guide, which systematic reviews will be chosen, how their credibility will be evaluated, and how the quality of the body of evidence will be rated. Data will be synthesised into an evidence map that will present a matrix that depicts each available treatment for stable COPD with a quantitative estimate on symptoms/outcomes from the patient perspective, along with an indication of the size and certainty in the evidence. Ethics and dissemination Approval by a research ethics committee is not required since the review will only include published data. The systematic review will be published in a peer-reviewed journal. PROSPERO registration number CRD42018095079

Background: In the busy world of cardiovascular medicine, abstracts may be the only part of a publication that clinicians read. Therefore, it is critical for abstracts to accurately reflect article content. The extended CONSORT (Consolidated Standards of Reporting Trials) Statement for Abstracts was developed to ensure high abstract quality. However, it is unknown how often adherence to CONSORT guidelines occurs among cardiovascular journals. Methods and Results: We searched MEDLINE for randomized controlled trials published in 3 major cardiovascular journals ( Circulation, Journal of the American College of Cardiology , and European Heart Journal ) from 2011 to 2017. Post hoc, interim, and cost-effective analyses of randomized controlled trials were excluded. Two independent investigators extracted the data using a prespecified data collection form and a third investigator adjudicated the data. The primary outcome was frequency of subcategory adherence to CONSORT guidelines. A total of 478 abstracts were included in the analysis. Approximately half of the abstracts (53%; 255/478; 95% CI, 49%–57%) identified the article as randomized in the title. All abstracts detailed the interventions for both study groups (100%) and 81% (95% CI, 78%–85%) reported trial registration. Methodological quality reporting was relatively low: 9% (45/478; 95% CI, 6%–12%) described participant eligibility criteria with settings for data collection, 43% (204/478; 95% CI, 39%–47%) reported details of blinding, and <1% (4/478; 95% CI, 0%–2%) reported allocation concealment. Approximately 60% (301/478; 95% CI, 59%–67%) of the included abstracts provided primary outcome results while 55% (262/478; 95% CI, 51%–60%) reported harms or adverse effects. Conclusions: There is a high prevalence of nonadherence to CONSORT guidelines among leading cardiovascular journals. Efforts by editors, authors, and reviewers should be made to increase adherence and promote transparent and unbiased presentation of study results.