Citations

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

4009 Background: Interim analysis of a global, phase 2 KEYNOTE-059 study (NCT02335411) reported manageable safety and promising antitumor activity for pembro alone or pembro + chemo in pts with G/GEJ cancer. Here we report long-term efficacy and safety data of all cohorts. Methods: Pts with recurrent or metastatic G/GEJ adenocarcinoma were enrolled in 3 cohorts. Cohort 1 pts (PD-L1–positive or –negative) received pembro alone after ≥2 prior lines of therapy. Cohort 2 pts (PD-L1–positive or –negative) received pembro + cisplatin (80 mg/m2 day 1) + 5-fluorouracil (800 mg/m2 days 1-5 Q3W) or capecitabine (in Japan only, 1000 mg/m2 twice daily) as first-line. Cohort 3 pts (PD-L1–positive, combined positive score ≥1% using the PD-L1 IHC 22C3 pharmDx assay) received pembro alone as first-line. All pts received pembro 200 mg Q3W for up to 2 years. End points included safety, ORR, DOR, and OS. Results: At data cutoff (Aug 8, 2018), median (range) follow-up was 6 (1-38), 14 (2-40), and 21 (2-36) months for cohorts 1 (n = 259), 2 (n = 25), and 3 (n = 31), respectively. In cohort 1, confirmed ORR (95% CI) was 11.6% (8-16) overall, 15.5% (10-22) in PD-L1–positive, and 6.4% (3-13) in PD-L1–negative tumors. In cohort 2, confirmed ORR was 60.0% (39-79) overall, 73.3% (45-92) in PD-L1–positive, and 37.5% (9-76) in PD-L1–negative tumors. In cohort 3, confirmed ORR was 25.8% (12-45). Median (range) DOR in months was 16.1 (2-35+), 4.6 (3-37+), and not reached (2.1-32.5+) in cohorts 1, 2, and 3, respectively. OS at 1 year/2 years was 24.6%/12.5%, 52%/32%, and 63.6%/40.1% in cohorts 1, 2, and 3, respectively. In cohorts 1, 2, and 3, grade 3-5 treatment-related adverse event (TRAE) incidence was 46 (18%), 20 (80%), and 8 (26%) respectively. TRAEs led to discontinuation in 6 (2%) and 3 (12%) pts in cohorts 1 and 2, respectively, and to death in 2 (1%) pts in cohort 1. No TRAEs led to discontinuation or death in cohort 3. Conclusions: These updated results demonstrate manageable safety, durable clinically meaningful activity of pembro in heavily pretreated pts, and promising efficacy of first-line pembro (alone or + chemo) in pts with advanced G/GEJ cancer. Clinical trial information: NCT02335411.

TPS2656 Background: ESCC remains the predominant histological subtype of, and accounts for most deaths from, esophageal cancer. PD-1 inhibition has demonstrated antitumor activity and was generally well tolerated in patients (pts) with advanced unresectable or metastatic ESCC. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Results from early phase clinical studies suggest single-agent tislelizumab was generally well tolerated and had antitumor activity in pts with solid tumors, including ESCC. Methods: This phase 3, randomized, placebo-controlled, double-blind study (NCT03783442) is designed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment of unresectable, locally advanced recurrent or metastatic ESCC. Adult pts with histologically confirmed ESCC that had metastatic disease either at first diagnosis or with a ≥6 month treatment-free interval will be eligible. Additional eligibility criteria include measurable/evaluable disease, ECOG performance score ≤1, and no prior anti-PD-(L)-1, PD-L2, or other first-line therapy or palliative radiation treatment ≤4 weeks before treatment. Approximately 480 pts will be randomized 1:1 to receive investigator-chosen chemotherapy (ICC) plus tislelizumab 200 mg IV Q3W or ICC plus placebo. Chemotherapy options include: platinum (cisplatin 60–80 mg/m2 or oxaliplatin 130 mg/m2 IV Q3W) plus 5-FU 750–800 mg/m2 IV daily for 5 days Q3W; or platinum plus capecitabine 1000 mg/m2 orally BID for 14 days Q3W; or platinum + paclitaxel 175 mg/m2 IV Q3W. Progression-free survival and overall survival are coprimary endpoints; secondary endpoints include objective response rate, duration of response, and health-related quality-of-life. Safety will be assessed by monitoring adverse events, physical examinations, vital signs, and electrocardiograms. This study is actively enrolling. Clinical trial information: NCT03783442.

Abstract Introduction Flight surgeons play a vital role in U.S. Air Force aviation operations by ensuring that pilots are medically prepared to meet the demands of military aviation. However, there is natural tension between pilots and flight surgeons. A pilot may be reluctant to share medical information with a flight surgeon who could negatively impact the pilot’s career or flight status. In this preliminary study, we sought to identify pilot-perceived strengths and weaknesses in the relationship between U.S. Air Force aviators and their flight surgeons. Materials and Methods An online survey regarding pilot–flight surgeon confidence and perceived values was distributed electronically to a convenience sample of U.S. Air Force aviators. Participants included U.S. Air Force active duty and Air Reserve Component (Air Force Reserve and Air National Guard) military aviators in addition to U.S. Air Force Academy aviation cadets. Results One hundred and seventy-three aviators participated in the survey. Respondents reported variable comfort in approaching flight surgeons with medical concerns and suggested that they believed other pilots might be withholding medical information from flight surgeons or seeking care from civilian physicians for career protection. Conclusions We sought to examine the pilot–flight surgeon relationship and its impact on daily flying operations. While limited, results suggest that there may be gaps in trust between pilots and their flight surgeons. These findings could present an opportunity to improve the pilot–flight surgeon relationship by identifying factors that contribute to closer pilot–flight surgeon relationships.

Purpose: The purpose of this article is to provide a data-driven set of best practices to consider in the management of diabetic macular edema (DME). Methods: The current discussion and recommendations represent the authors’ interpretations of data from selected references based on perceived relevance and study design. Results: DME is a common cause of visual impairment globally. The underlying progressive retinal microvascular damage is associated with upregulation of VEGF and a multitude of other inflammatory pathways. Three clinically relevant subcategories of DME can be identified: central-involved DME (CIDME) with preserved visual acuity, CIDME with associated visual loss, and non-CIDME. Management approaches may include observation, laser photocoagulation, intravitreal pharmacotherapy with anti-VEGF agents or corticosteroids, or a combination of these, and may vary depending on the specific type of DME and associated severity of diabetic retinopathy. Additional factors to consider in the management of patients with DME include the appropriate use of imaging and recognition of the chronic nature of the underlying disease process in many eyes. Conclusions: DME management is complex. Intravitreal pharmacotherapies are the current cornerstone of treatment for CIDME and appear poised to remain so for the foreseeable future.

Objectives Remote ischemic preconditioning has been proposed as a possible potential treatment for ischemic stroke. However, neuroprotective benefits of the pre-procedural administration of remote ischemic preconditioning have not been investigated in patients undergoing an elective endovascular intracranial aneurysm repair procedure. This study investigated the safety and feasibility of remote ischemic preconditioning in patients with an unruptured intracranial aneurysm who undergo elective endovascular treatment. Methods In this single-center prospective study, patients with an unruptured intracranial aneurysm undergoing elective endovascular treatment with flow diverters or coiling were recruited. Patients received three intermittent cycles of 5 minutes arm ischemia followed by reperfusion using manual blood cuff inflation/deflation less than 5 hours prior to endovascular treatment. Patients were monitored and followed up for remote ischemic preconditioning-related adverse events and ischemic brain lesions by diffusion -weighted magnetic resonance imaging within 48 hours following endovascular treatment. Results A total of seven patients aged 60 ± 5 years with an unruptured intracranial aneurysm successfully completed a total of 21 sessions of remote ischemic preconditioning and the required procedures. Except for two patients who developed skin petechiae over their arms, no other serious procedure-related adverse events were observed as a result of the remote ischemic preconditioning procedure. On follow-up diffusion -weighted magnetic resonance imaging, a total of 19 ischemic brain lesions with a median (interquartile range) volume of 245 (61–466) mm 3 were found in four out of seven patients. Conclusions The application of remote ischemic preconditioning prior to endovascular intracranial aneurysm repair was well tolerated, safe and clinically feasible. Larger sham-controlled clinical trials are required to determine the safety and efficacy of this therapeutic strategy in mitigating ischemic damage following endovascular treatment of intracranial aneurysms.

Venous thromboembolism (VTE) and coronary artery disease are major health issues that cause substantial morbidity and mortality. New data have emerged suggesting that these two conditions could have a close relationship. Thus, we sought to determine the trends in annual rate of VTE occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and measure its impact on in-hospital mortality, bleeding complications, and cost and length of hospitalization. We queried the 2003–2013 Nationwide Inpatient Sample databases to identify adults with primary diagnosis of STEMI. VTE events were then allocated. Inpatient outcomes of patients with VTE were compared to those without VTE. Out of 2,495,757 hospitalizations for STEMI, VTE was diagnosed in 25,149 (1%) hospitalizations. Patients who experienced VTE were older (mean age: 67.5 vs 64.8, p < 0.01) and had a higher proportion of black patients (10.1% vs 7.7%, p < 0.001) and females (40.1% vs 35%, p < 0.001) compared to patients without VTE. There was an increasing trend in the rate of VTE during the study period (2003: 0.8% vs 2013: 1.0%, p < 0.001). Patients with VTE had a prolonged hospitalization (median: 9 vs 3 days, p < 0.001), increased cost, higher risk of gastrointestinal bleeding (OR: 2.13, p < 0.001), intracranial hemorrhage (OR: 2.14, p < 0.001), blood transfusions (OR: 1.94, p < 0.001), and mortality (OR: 1.39, p < 0.001). The rate of VTE occurrence in patients with STEMI in our study was 10 per 1000 admissions. VTE was associated with more bleeding complications, longer hospital stays, higher costs, and mortality. These findings suggest that a more aggressive approach for VTE prophylaxis may be warranted in this population.