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Decades after the introduction of oral anti-coagulants namely the vitamin K antagonist (VKA) Warfarin and antiplatelet agents such as Aspirin and Plavix, new classes of direct, small molecule, novel oral anti-coagulant medications and antiplatelet P2Y12 receptor inhibitors have recently become available. For the novel oral anticoagulants (NOAC), these agents can be separated by direct thrombin inhibitors such as Dabigatran and direct Factor Xa inhibitors such as Rivaroxaban and Apixaban. For next generation antiplatelet agents such as Ticagrelor and Prasugrel, these new P2Y12 receptor inhibitors form the cornerstone of therapy for patients with acute coronary syndrome (ACS) or undergoing percutaneous interventions. These novel oral antithrombotics are revolutionizing the field of stroke prevention, atrial fibrillation (AF), the management of venous thromboembolism (VTE) and treatment of ACS. This article reviews the current research developed in order to identify therapeutic effects and establish net clinical benefits of these new oral antithrombotics.

The mTOR inhibitors everolimus and temsirolimus significantly increased the risk of high-grade stomatitis in cancer patients. Efforts towards the prevention, treatment, and identification of individuals at risk may allow for improved quality of life and consistent dosing.

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Background. The objective of our study was to ascertain racial/ethnic disparities in Asian/Pacific Islanders (API) for non-small-cell lung cancer (NSCLC) clinicopathologic features and survival outcomes based on various tumor characteristics and treatment modalities. Method. SEER database identified invasive NSCLC cases from 2004 to 2010. Variables included American Joint Committee on Cancer (AJCC) stage 7, tumor grade, tumor size, histology, age, marital status, radiation, surgery, and reason for no surgery. The Kruskall-Wallis test and the Z test were used to examine differences between races/ethnicities and the referent, non-Hispanic white (NHW). Multivariate Cox proportional analyses were used to establish the weight of the prognostic significance contributing to disease-specific survival (DSS) in each AJCC stage. Result. Improved DSS was seen in API across stage I (HR: 0.78), stage II (HR: 0.79), and stage IV (HR: 0.86), respectively, compared to the referent NHW (P < 0.01). Prognosis was improved by being married, being female gender, AIS histology, and birth outside the US (P < 0.01). Conclusion. We have demonstrated improved survival among API in early stage and stage IV NSCLC. Further research is necessary to clarify the role of lifestyle and tumor biology for these differences.

Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.

Introduction: DAC is a hypomethylating agent FDA approved for the treatment of advanced myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).Despite its clinical activity, the duration of response is limited and prognosis at relapse is poor. In pre-clinical studies, we identified potent epigenetic effects of ATO alone and in combination with DAC, and also found that carboplatin (Carbo) can enhance gene reactivation in combination with DAC. We therefore initiated a randomized phase 2 clinical trial (NCT02188706) to compare the safety and efficacy of DAC in combination with either Carbo or ATO as compared to single agent DAC in patients with MDS/CMML and Acute Myeloid Leukemia. Here we present updated results for the MDS/CMML cohort. Methods: Patients with MDS/CMML INT-1 were randomized to one of three regimens: DAC 20 mg/m2 days 1-5, (DAC), DAC as above and Carbo AUC 5 on day 8 (DAC/Carbo), or DAC as above and ATO 0.15 mg/kg days 1-5 (DAC/ATO). We used adaptive randomization based on response rate which started after 10 patients were equally randomized to each arm. Cycles were scheduled every 28 days for a minimum of 4 cycles. Dose reductions/delays were allowed based on response and tolerability. Patients remained on treatment as long as they continued to benefit without toxicity. The primary endpoint was the composite response rate: the complete response (CR: complete response, mCR: marrow complete response and CRi: complete response with incomplete blood count recovery) and partial response (PR) rates using the modified IWG 2006 criteria. Secondary endpoints included median overall survival (OS) and safety. DNA methylation changes were measured using LINE1 bisulfite/pyrosequencing. Results: As of July 2016, 42 patients (MDS = 40, CMML=2) have been enrolled on study. Median age was 71 years (range, 35 to 84 years). There was no statistically significant difference in patients' characteristics between the three arms. Median number of cycles for the treatment arms was 4 (range, 1-15). Response data was evaluable for 36 patients (8 on DAC alone, 5 on DAC/Carbo and 23 on DAC/ATO). Composite responses were seen in 3/8 patients on DAC (37.5%), 0/5 patients on DAC/Carbo (0%, p=0.23 compared to DAC alone) and 12/23 patients on DAC/ATO (52.2%, p=0.69 compared to DAC alone). Median OS among MDS/CMML patients receiving DAC/ATO (17.8 months) was improved compared to the DAC/Carbo (3.9 months) and DAC (9.8 months) arms (p=0.01) [Figure 1]. There was not a significant difference in high-grade (≥ grade 3) toxicity between the three arms, with grade 3 neutropenia and thrombocytopenia as the most common side effects. DNA methylation analysis showed equivalent demethylation in all the arms, suggesting that the epigenetic effects of ATO were independent of DNA methylation, which was consistent with pre-clinical studies. Conclusion: Our results demonstrate higher response rates and a significant survival benefit with the combination of DAC and ATO in comparison to DAC alone in patients with MDS/CMML. Disclosures Kropf: Celgene: Consultancy; Takeda: Consultancy. Fung:Amgen: Consultancy; Genzyme: Consultancy. Kantarjian:ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Issa:Astex Pharmaceuticals: Consultancy; Teva Pharmaceutical Industries: Consultancy.

Background. Inhibitors of the mammalian target of rapamycin (mTOR) are currently approved for the treatment of several cancers, and their use is associated with serious rash, which affects patient ' s quality of life and leads to undesirable dose reductions or interruptions. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the overall risk of developing high-grade rash with mTOR inhibitors in cancer patients. Methods. We searched the PubMed database and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings up to December 2013 for relevant studies. Eligible studies included RCTs in which everolimus or temsirolimus was compared to controls in cancer patients. The summary incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a random-or fi xed-effects model depending on the heterogeneity of the included trials. Results. A total of 11 RCTs with 4752 patients (mTORs: 2725, controls: 2027) with a variety of solid tumors were included in the analysis. The incidences of all-grade (grade 1 -4) and high-grade rash (grade 3 -4) were 27.3% (95% CI 21.0 -34.7%) and 1.0% (95% CI 0.6 -1.4%), respectively. In comparison with controls, mTOR inhibitors signifi cantly increased the risk for developing all-grade rash (RR ϭ 3.55, 95% CI 3.0 -4.20, p Ͻ 0.001) and high-grade rash (RR ϭ 4.25, 95% CI 1.63 -11.10, p ϭ 0.003). The increased risk of high-grade rash did not vary signifi cantly among different tumors (p ϭ 0.91). There was no signifi cant difference between everolimus and temsirolimus (p ϭ 0.60). There was also no signifi cant difference between mTOR inhibitors alone and in combination with other agents (p ϭ 0.57). Conclusions. Everolimus and temsirolimus signifi cantly increased the risk of high-grade rash in cancer patients. Early recognition and appropriate treatment is recommended.