scholarly journals Safety of Direct Acting Oral Anticoagulants (DOACs) in Comparison to Low Molecular Weight Heparin (LWMH) in Gastrointestinal and Genito-Urinary Cancers

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1070-1070
Author(s):  
Shafia Rahman ◽  
Juan Trias ◽  
Margarita Kushnir ◽  
Henny H. Billett
Keyword(s):  
Major Bleeding ◽  
Bleeding Event ◽  
Categorical Variables ◽  
Tumor Site ◽  
Bleeding Events ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
Cancer Types ◽  
Gi Cancers ◽  
Cancer Associated Thrombosis

Abstract Introduction: DOACs are absorbed in the gastrointestinal (GI) tract and DOAC elimination is primarily through the GI and genitourinary (GU) systems. The safety of DOACs in cancer associated thrombosis in subjects with malignant lesions in GI and GU malignancies has been of concern. Studies have been sparse and data conflicting. Methods: We identified patients with active GI and GU malignancies from July 2001 to July 2020 with confirmed VTE at our institution. Patients who received either enoxaparin or a DOAC (apixaban or rivaroxaban) were included in the study. Demographic, disease characteristics, VTE data and events were extracted from electronic medical records (EMR). Date of anticoagulation (AC) initiation was based on the first order and/or prescription of the anticoagulant. Patients were followed either to the earliest bleeding event (BE) or one year from initiation, whichever occurred first. BEs were categorized based on ISTH guidelines. Variables were compared between LMWH and DOAC cohorts, as well as between the apixaban and rivaroxaban cohorts, using t-tests for continuous variables and chi-squared tests or Fisher's exact test for categorical variables. Results: We identified a total of 206 patients, 159 in the DOAC and 47 in the LWMH groups. Table 1 describes the baseline characteristics of the study populations. Median age of patients, gender and BMI were comparable for all groups. When evaluated for type of cancer, 66.6% of patients had active GI malignancy while 33.3% had active GU tumors. The majority of the patients given DOACs had a better ECOG status than those in the LMWH group (p=0.0023), but no difference was noted for ECOG status between DOACs (p=0.69). Most patients had metastatic disease. The majority of the VTE events were in the form of DVTs. Concomitant aspirin intake was 9.4% in DOAC and 4.2% in LMWH groups. Cancer subtypes and AC choice data are given in detail in Table 2. LMWH use was higher in blacks and somewhat lower in the Hispanic population (Table 1). When anticoagulation choice was examined by primary tumor site (Table 2), disproportionately more patients with GU tumors were placed on LMWH while more GI cancers were given a DOAC (p=0.014). Extent and stage of the cancer did not appear to bias anticoagulant choice (p=0.62). Within the DOACs, rivaroxaban use was higher in the GI cancers but considerably less used in the GU malignancies (p=0.00049). There was one recurrent thrombosis in each of the apixaban (1/86) and the rivaroxaban (1/73) cohorts. There were no recurrent events in the LMWH (0/47) cohort. The majority of patients in the DOAC and LMWH groups, 88.1% and 86.4%, had no CRNMB or major bleeding events in the 1-year period after the initiation of the therapeutic AC (Table 3). Combined BE (clinically relevant non-major bleeding [CRNMB] and major bleeding rates) with apixaban, rivaroxaban and LMWH were 17.4% (15/86), 20.5% (15/73), and 19.1% (9/47) respectively. There were no fatal bleeding episodes in any of the groups. Most of the bleeding events on DOACs and LMWHs occurred in the same organ system as the primary cancer (Table 3) but there was no statistically significant difference in bleeding events between patients on DOACs or LMWH for GI, GU or all cancer types (p=0.63, 0.75 and 0.97 respectively). Within DOACs, we also noted no statistically significant difference in the bleeding events with apixaban as compared to rivaroxaban in patients with GI primary, GU primary or all cancer types together, (p=0.47, 0.94 and 0.62 respectively). Conclusion: No significant differences in major/CRNM bleeding events were found for patients with GI or GU cancer associated thrombosis given DOACs (apixaban/rivaroxaban) vs enoxaparin. The tumor site is often the site of bleeding, but no differences in tumor-specific site bleeding could be shown by anticoagulant choice. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 80-80
Author(s):  
Jang Ho Cho ◽  
Sung Won Lim ◽  
Seung Tae Kim ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Her2 Status ◽  
Tumor Site ◽  
Diffuse Type ◽  
Disease Extent ◽  
Primary Tumor Site ◽  
Epithelial Cancers ◽  
Significant Difference ◽  
Cancer Types ◽  
Tumor Types

80 Background: Alterations in claudin expression can impair tight junction functioning, influence signaling pathways, and act as a tumor promoting event in some epithelial cancers. Recently, IMAB362, a highly potent and tumor cell-selective therapeutic antibody to claudin 18.2, has been developed and investigated in clinical trials. Methods: We prospectively conducted claudin 18.2 immunohistochemistry on 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Results: Most patients (414/430, 96.2%) were evaluable for claudin 18.2 expression by immunohistochemistry. In total, 4.1% (17/414) were deemed claudin 18.2+, including patients with pancreatic (16.7%, 1 of 6), gastric (14.1%, 12 of 85), biliary tract (6.3%, 1 of 16), genitourinary/miscellaneous (2.2%, 1 of 46), and colorectal (0.9%, 2 of 203) cancers. Twelve of 17 patients positive for claudin 18.2 had gastric cancers; this subgroup showed no statistical difference by gender, age, disease extent, primary tumor site, pathologic differentiation, HER2 status, or EBV status with or without claudin 18.2 expression. However, claudin 18.2 was more frequently positive in intestinal-type compared to diffuse-type by Lauren classification (p = 0.026). There was no significant difference in overall survival between patients with and without claudin 18.2 expression (p = 0.101). Conclusions: Our results add to the emerging literature on claudin 18.2 expression in various cancer types and support the need for extended clinical exploration of IMAB362.

scholarly journals Thromboprophylactic Efficacy and Safety of Anticoagulants After Arthroscopic Knee Surgery: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 25 ◽  
pp. 107602961988140
Author(s):  
Yang Yu ◽  
Shitao Lu ◽  
Jinpeng Sun ◽  
Wei Zhou ◽  
Hongjian Liu
Keyword(s):  
Major Bleeding ◽  
Bleeding Event ◽  
Control Group ◽  
Controlled Trials ◽  
Number Needed To Treat ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Increased Risk ◽  
Significant Difference

To examine the efficacy and safety of anticoagulants after knee arthroscopy (KA), PubMed, EMBASE, databases of Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure were searched up to August 2019 for randomized controlled trials (RCT). Seven RCTs including 4097 patients were demonstrated eligible according to the inclusion and exclusion criteria. The efficacy and safety of thromboprophylaxis were assessed and expressed using relative risk (RR) and 95% confidence intervals (95% CIs). The analysis of pooled data showed that anticoagulants group exhibited significant lower overall incidence of symptomatic and asymptomatic venous thromboembolism (VTE; RR = 0.35, 95% CIs: 0.22-0.55, P < .00001), significant higher incidence of all bleeding events (RR = 1.42, 95% CIs: 1.08-1.86, P = .01) compared to control group. However, no significant difference was found in terms of incidence of symptomatic VTE (RR = 0.43, 95% CIs: 0.15-1.21, P = .11) and incidence of major bleeding events (RR = 1.87, 95% CIs: 0.40-8.67, P = .42). The pooled number needed to treat to prevent one symptomatic or asymptomatic VTE was 26, while the pooled number needed to harm to cause one major bleeding event was 869. These results show that anticoagulants can effectively reduce the overall risk of VTE after KA; however, the increased risk of bleeding should be fully considered. Further studies are required to address the risk–benefit calculus and cost-effectiveness of anticoagulants after KA.

scholarly journals Concurrent Treatment of VEGFR Tyrosine Kinase Inhibitors (TKIs) and Factor Xa Inhibitors Is Associated with Increased Bleeding Risks

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3681-3681
Author(s):  
Sandip Patel ◽  
Tiffany George ◽  
Tzu-Fei Wang ◽  
Sherry Mori Vogt ◽  
Edmund Folefac ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Metastatic Cancer ◽  
Bleeding Event ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Factor Xa Inhibitor ◽  
Bleeding Events ◽  
Concurrent Treatment ◽  
Clinically Significant

ABSTRACT Background: Some cancer patients with thromboembolism require dual treatment of VEGFR TKIs and factor Xa inhibitors (direct or indirect), which may contribute to increased bleeding risks. However, the safety of such combination treatment has not been well characterized in the literature or national guidelines. Methods: This is a single center retrospective study, where we identified metastatic cancer patients (renal cancer, colorectal cancer, sarcoma, etc) who received concurrent VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib or cabozantinib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs] including rivaroxaban or apixaban) at the Ohio State University Medical Center. We assessed bleeding risks of dual therapies vs. factor Xa inhibitors alone, using the same patients as self controls. We reviewed medical charts of all identified patients for clinically significant bleeding events (defined as combined major bleeding and clinically relevant non-major bleeding by the International Society of Thrombosis and Haemostasis criteria). The Cox proportional hazard model was used to compare the differences of time to first clinically significant bleeding event between the groups of concurrent use and anticoagulant use only. Results: A total of 86 patients (26 females and 60 males) were included: 78 Caucasians, 6 African Americans, and 2 others. 81 patients had concurrent TKI and LMWH treatment; 20 patients had concurrent TKI and DOACs; and 85 patients have had been on factor Xa inhibitor alone (LMWH or DOACs) at some point. Some patients had been on both LMWH and DOACs at different time periods. Overall, there were 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment and 17 events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days (52 days for concurrent treatment and 99 days for Xa inhibitor alone). In this self-control study, concurrent treatment was associated with a statistically higher risk of clinically significant bleeding events (HR, 2.84; 95% CI, 1.43-5.64, P &lt; 0.01), which reached 37% patient population in the first 3 months, while the bleeding associated with factor Xa inhibitor alone seemed spaced out at the entire length of anticoagulation (8% by 6 months). Similar trend was found in the analysis of patient group of concurrent TKI and LMWH vs. LMWH alone (HR, 1.96; 95% CI, 0.95-4.02, P = 0.067), although significance was not reached likely due to insufficient power. Sample size was inadequate for meaningful comparison between concurrent VEGFR TKI and DOAC vs. DOAC alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with a significantly increased bleeding risks when compared with factor Xa inhibitors alone in patients with metastatic cancer. Disclosures No relevant conflicts of interest to declare.

Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.

1997 ◽  
Vol 15 (8) ◽  
pp. 2792-2799 ◽  
Author(s):  
A Gajjar ◽  
R A Sanford ◽  
R Heideman ◽  
J J Jenkins ◽  
A Walter ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cerebral Hemisphere ◽  
Young Patients ◽  
Age At Diagnosis ◽  
Cerebellar Hemisphere ◽  
Low Grade ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
The Impact

PURPOSE To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. PATIENTS AND METHODS Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four. RESULTS The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors. CONCLUSION The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.

P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ishigami ◽  
Y Aono ◽  
S Ikeda ◽  
K Doi ◽  
Y An ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Platelet Count ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Bleeding Events ◽  
Major Bleeding Event ◽  
Entire Cohort ◽  
Severe Group ◽  
The Mean

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p<0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p<0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p<0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p<0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

Major Bleeding with Ibrutinib: More Than Expected

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3229-3229 ◽  
Author(s):  
Paul R Kunk ◽  
Joesph Mock ◽  
Michael E. Devitt ◽  
Surabhi Palkimas ◽  
Jeremy Sen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Event ◽  
Lymphocytic Leukemia ◽  
Significant Activity ◽  
University Of Virginia ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Introduction: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has significant activity in treating lymphoma. While approved for patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), its activity in other lymphomas and solid tumors is under investigation and its use is increasing dramatically. Overall it is well tolerated compared to chemotherapy, but bleeding has emerged as a common adverse event with rates as high as 50% and major bleeding around 3% (Jones, abstract #1990, 2014 ASH Annual Meeting). As the use of ibrutinib increases outside of a clinical trial setting, the rate of major bleeding is likely to rise. Methods: To better understand the risk of bleeding in ibrutinib treated patients, we reviewed all patients at the University of Virginia and satellite clinics who were treated with ibrutinib between January 2012 and May 2016. Patients were required to be treated for at least 1 month with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, ibrutinib indication and dose, length of treatment, concurrent medications, blood tests and bleeding events. All forms of anti-platelets and anticoagulants drugs, as well as medications interacting with cytochrome P450 3A4 (3A4), which metabolizes ibrutinib, were recorded. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators. Results: Eighty-nine patients were identified. Eighteen patients were excluded for insufficient follow up leaving 71 patients for analysis. Median age was 73 years old (44-92) with 74% male. The most common indications for treatment were CLL (65%) and MCL (27%). Most patients were treated with either 420mg (64%) or 560mg (21%). Median length of time on ibrutinib was 412 days, most with ongoing use at time of data collection. Seventy percent of patients were also treated with an anti-platelet medication, mostly aspirin for CAD with several patients on multiple anti-platelet medications. Seventeen percent were treated with an anti-coagulant, mostly apixaban for atrial fibrillation. Thirteen percent of patients (9/71) were treated with combined anti-platelet and anti-coagulant medications. Ten percent of patients were treated with a medication that has a moderate or strong interaction with 3A4. Bleeding of any grade occurred in 56% of patients, mostly bruising and epistaxis. Major bleeding, defined as grade 3 or higher, occurred in 18% of patients. Three patients developed major bleeding after an invasive procedure without ibrutinib being held. One patient died as a result of peri-procedural bleeding. Of the 9 patients treated with combined anti-platelet and anti-coagulant therapy, 78% suffered a major bleeding event. Of the ten patients on ibrutinib alone, without concurrent use of an anti-platelet, anti-coagulant or 3A4 drug interaction, no major bleeding events occurred. Conclusion: In this study examining real world use of ibrutinib, the rates of major bleeding are higher than previously reported. Most patients who suffered major bleeding were also treated with an anti-coagulant and/or anti-platelet medication. As the use of ibrutinib increases outside of clinical trials, a careful review of medications should be performed in addition to adherence to perioperative drug withholding guidelines. Patients requiring anti-coagulant and/or anti-platelet medications while on ibrutinib need careful consideration of the risks and benefits given the higher incidence of bleeding in this population. Table 1 Table 1. Disclosures Portell: AbbVie: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Acerta: Research Funding. Williams:Janssen and Pharmacyclics: Research Funding; University of Virginia: Employment.

Major Bleeding Complications Among Patients Treated with Ibrutinib and Concomitant Antiplatelet, Anticoagulant, or Supplemental Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4387-4387 ◽  
Author(s):  
Aaron Pavlik ◽  
Hallie Barr ◽  
Emily Dotson ◽  
John C. Byrd ◽  
Kristie A. Blum ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Event ◽  
Antiplatelet Agents ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Major Bleeding Events

Abstract Background: Ibrutinib, an orally bioavailable small molecular inhibitor of Bruton's tyrosine kinase (BTK), is an approved therapy for chronic lymphocytic leukemia (CLL), relapsed mantle cell lymphoma (MCL) and Waldenstrӧm's macroglobulinemia (WM). Beyond B lymphocytes, BTK signaling is important for collagen-mediated platelet activation, and BTK inhibition has been associated with primary hemostatic bleeding events (Levade et al Blood 2014). Although serious bleeding events have been uncommon (1-5%) in clinical trial populations, there is limited data describing the potential for increased serious bleeding incidence when ibrutinib is co-administered with other agents affecting the clotting cascade or platelet function. Methods: We conducted a retrospective cohort study to evaluate the incidence of major bleeding in patients receiving ibrutinib concomitantly with antiplatelet agents (non-steroidal anti-inflammatory agents, ADP inhibitors), anticoagulants (heparins, warfarin, novel oral anticoagulants), or supplements with potential anticoagulant activity (vitamin E and fish oil). Major bleeding events were identified using criteria developed by the International Society on Thrombosis and Haemostasis (Schulman et al J Thromb Haemost 2005). Patients 18-89 years of age and treated with ibrutinib for CLL, MCL, or WM between March 1, 2010 and March 1, 2015 were included. The primary endpoint of this study was the incidence of major bleeding events, but we also sought to identify risk factors associated with the development of major bleeding, focusing on potential drug interactions. Based on the historic prevalence of major bleeding in ibrutinib clinical studies, we calculated that at least 20 major bleeding events would need to be identified in order to perform blinded multinomial regression on the collected data of an estimated 400 patients. Results: 437 eligible patients were included in the analysis. Patients were overwhelmingly male (71.4%) and white (94.8%), with a mean age of 67.1 years (range: 29-89). 53.1% received ibrutinib as participants of a clinical trial, and the remainder received standard-of-care ibrutinib treatment. The table (upper panel) summarizes use of concomitant antihemostatic agents by presence or absence of major bleeding events. Characteristics of the major bleeding events are further detailed in the lower panel. The most commonly observed concomitant antihemostatic medication was aspirin, with 147 patients (33.6%) being exposed to aspirin within the study period. Fourteen instances of major bleeding were observed, corresponding to an overall incidence of 3.2%. These major bleeding events all occurred in CLL patients receiving ibrutinib at the standard dose of 420 mg daily. Two patients had platelet counts less than 50 k/µL at time of the bleeding event. One-half of the major bleeding events were observed in the absence of an antihemostatic medication, and 2 of the observed major bleeding events resulted in death (1 received concomitant warfarin). Fourteen patients (3.3%) in the group without major bleeding were on anticoagulation, 4 being warfarin. The most common sites of major bleeding were gastrointestinal (50%), intracranial (14.3%) and thoracic (14.3%). While most patients developing major bleeding permanently discontinued ibrutinib (57.1%), approximately one third of the patients who developed major bleeding subsequently resumed ibrutinib following resolution of the bleeding event. Subsequently, these patients did not experience a recurrent major bleeding event. The rate of major bleeding did not meet power to detect statistical differences in bleeding events when comparing concomitant therapy, Conclusions: Our observed incidence of major bleeding is consistent with previous controlled clinical trials, suggesting similar safety profile when ibrutinib is used outside of a controlled setting. Major bleeding events were uncommon despite the frequent co-administration of antiplatelet agents. However, because we modified practice early to avoid therapeutic anticoagulation during ibrutinib therapy whenever possible, the number of patients receiving such drugs in combination was small and precludes inferences regarding safety. Table Table. Disclosures Blum: Pharmacyclics: Research Funding. Awan:Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Woyach:Acerta: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding. Christian:Pharmacyclics: Research Funding; Janssen: Research Funding. Jones:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding.

A phase I feasability study of concurrent fondaparinux (F) with carboplatin (Crb) and paclitaxel (P) for metastatic non-small cell lung cancer (NSCLC): An analysis of coagulation/angiogenic biomarker (CABM) kinetics.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19143-e19143
Author(s):  
David James Mooney ◽  
Debi Miley ◽  
Mary Jerome ◽  
Stefan C. Grant ◽  
Francisco Robert
Keyword(s):  
Major Bleeding ◽  
Metastatic Cancer ◽  
Bleeding Event ◽  
Stage Iv ◽  
Endothelial Damage ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Angiogenic Biomarkers

e19143 Background: There is an association between risk of thrombosis and metastatic cancer. Chemotherapy (C) also independently increases thrombotic risk. This increased risk is multifactorial, including endothelial damage and release of angiogenic cytokines. We hypothesized that adding anticoagulation to C may decrease thrombotic risk and also, potentially, have anti-tumor effect. Methods: The primary aim of this study was to determine the tolerability and safety (bleeding events) of the combination of F with 21-day cycle chemotherapy (Crb AUC 6 + P 200 mg/m2) in two cohorts of untreated patients (pts) with stage IV NSCLC. The secondary objectives were to determine incidence of venous thrombosis (VT), changes in CABM parameters during treatment, and clinical efficacy endpoints. Two cohorts of pts received F from cycles 2-4 with Crb+P. Cohort A received 2.5 mg F daily from cycle 2-4. Cohort B received 7.5 mg of F on day 1, 2 of cycle 2-4 and 2.5 mg F on day 3-21. Results: Clinical data from 19 evaluable pts are as follows: median age 55 years, 63% male, and 32% adenocarcinoma. There was no major bleeding event (BE) in either cohort, and 5 pts had a minor BE. There was no VT. Median time to progression was 5 months (3.8-6.2 months), and overall survival was 10 months (4.3-15.6 months). Baseline values of sensitive markers of activated coagulation (D-Dimer, Thrombin Anti-Thrombin Complex) were above the normal range in most patients. These biomarkers tended to increase during the first cycle (without F); whereas the same markers decreased during the second cycle (with F). A reduction of the angiogenic biomarkers during therapy was observed with VEGF, TGF-β1, and Angiopoietin-1. Conclusions: Concurrent treatment with F and chemotherapy for metastatic NSCLC is feasible with no major bleeding and little minor bleeding. During chemotherapy, coagulant and angiogenic biomarkers tended to increase, perhaps suggesting an increase in thrombogenic state. When F was added, these markers trended downward, suggesting that the proangiogenic state associated with cancer may be significantly altered by anticoagulation. Clinical trial information: NCT00476216.

Outcomes of melanoma soft parts/clear cell sarcoma (MSP/CCS) patients (pts) with immune and targeted therapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21046-e21046
Author(s):  
Amy Little Jones ◽  
Aron Joon ◽  
Lauren Elaine Haydu ◽  
Alexander J. Lazar ◽  
Michael T. Tetzlaff ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Clear Cell Sarcoma ◽  
Tumor Site ◽  
Akt Inhibitor ◽  
Durable Response ◽  
Primary Tumor Site ◽  
Regional Metastases ◽  
Significant Difference

e21046 Background: Overall survival (OS) for pts with cutaneous melanoma has vastly improved with checkpoint inhibitors (CPI) and targeted therapy (TT), but less is known about outcomes of other rare tumors showing melanocytic differentiation. We examined outcomes for metastatic pts with MSP/CCS at MD Anderson (MDA) to characterize outcomes with contemporary therapies. Methods: Pts with MSP/CCS were identified in the MDA databases. Pts with < 2 visits to MDA or without molecular confirmation of dx were excluded. Log-rank testing was used to compare OS among distributions. Results: A total of 102 MSP/CCS pts were identified. Initial diagnosis was local disease 46%, regional metastases 34%, and systemic metastases 20%. Primary tumor site was lower extremity (LE) 48%, GI tract 29%, upper extremity (UE) 18%. 65 pts were diagnosed with metastatic disease (dz), including 32% with lung-only, 14% liver-only, and 51% with multiple metastatic sites. Median OS from diagnosis of distant metastatic dz was 22 mos (95% CI 16-34 mos). Primary tumor site (GI 46.4 vs. LE 19.1 vs. UE 14.7 mos; p = 0.018) and race (white 26.8 vs. black 6.5 mos, p = 0.019, HR 0.45) were significantly associated with OS from distant metastasis; sex, age, decade of diagnosis, size of primary, and prior treatment with neoadjuvant or adjuvant therapy were not. Treatments for metastatic dz included chemotherapy (n = 29), biochemotherapy (n = 11), biotherapy (n = 5), CPI (n = 11) and TT (n = 19). Median OS was 15.9 mos from start of CPI (range 10.7 to NR) and 16.9 mos from start of TT (range 7.8 to NR). Median OS from metastatic dz for pts not treated with CPI or TT was 17.1 mos (range 12.4 to 32.5), which was not significantly different versus CPI or TT. Duration of response was < 6 mos for 91% pts receiving CPI and 89% pts receiving TT. One pt had a durable response (41.8 mos) to anti-PD1 and one pt had a durable response (24.8 mos) to an AKT inhibitor. Conclusions: While rare responses to CPI and TT were observed, no significant difference was detected in OS compared to traditional therapies in pts with metastatic MSP/CCS. The development of more effective therapies remains an unmet need for this disease.

The impact of primary tumor site on outcomes of treatment with etoposide and cisplatin in grade 3 gastroenteropancreatic neuroendocrine carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 213-213
Author(s):  
Sang Eun Yoon ◽  
Jung Hoon Kim ◽  
Joon Young Hur ◽  
Su Jin Lee ◽  
Jeeyun Lee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Neuroendocrine Carcinoma ◽  
Primary Tumor ◽  
Medical Center ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
The Impact

213 Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited. Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated. Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (p = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites. Conclusions: Results from this study showed thatRR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.

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