Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.

signed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as

In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.

Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.

Objective To study the effect of the innate cytokine, MIF, on the susceptibility and the severity of SLE in a multinational population of Caucasian and African-American patients. Methods We studied the association between two functional polymorphisms in the MIF gene: a −794 CATT5-8 microsatellite repeat (rs5844572) and a −173 G/C SNP (rs755622), with SLE in 3195 patients and controls. We also measured MIF plasma levels in relation to genotypes, clinical phenotypes, and TLR 7-stimulated MIF production in vitro. Results Both Caucasians and African-Americans with the high expression, −794 CATT7/173*C haplotype had lower SLE incidence (OR 0.63 [0.53, 0.89], p=0.001 in Caucasians, and OR 0.46 [0.23, 0.95], p=0.012 in African-Americans). By contrast, among patients with established SLE, those with nephritis, serositis, and CNS involvement had reduced frequencies of low expression MIF genotypes (−794 CATT5) when compared to patients without end-organ involvement (p=0.005 for serositis, p=0.023 for nephritis, and p=0.04 for CNS involvement). Plasma MIF levels and TLR7 stimulated MIF production in vitro reflected the underlying MIF genotype of the studied groups. Conclusion These data suggest that MIF, which has both pro-inflammatory properties and macrophage and B cell survival functions, exerts a dual influence on the immunopathogenesis of SLE. High expression MIF genotypes are associated with a reduced susceptibility to SLE and may contribute to an enhanced clearance of infectious pathogens. Once SLE develops however, low expression MIF genotypes may protect from ensuing, inflammatory end-organ damage.

We present a detailed abundance analysis of the bright (V = 9.02), metal-poor ([Fe/H] = −1.47 ± 0.08) field red horizontal-branch star HD 222925, which was observed as part of an ongoing survey by the R-Process Alliance. We calculate stellar parameters and derive abundances for 46 elements based on 901 lines examined in a high-resolution optical spectrum obtained using the Magellan Inamori Kyocera Echelle spectrograph. We detect 28 elements with 38 ≤ Z ≤ 90; their abundance pattern is a close match to the Solar r -process component. The distinguishing characteristic of HD 222925 is an extreme enhancement of r -process elements ([Eu/Fe] = +1.33 ± 0.08, [Ba/Eu] = −0.78 ± 0.10) in a moderately metal-poor star, so the abundance of r -process elements is the highest ([Eu/H] = −0.14 ± 0.09) in any known r -process-enhanced star. The abundance ratios among lighter (Z ≤ 30) elements are typical for metal-poor stars, indicating that production of these elements was dominated by normal Type II supernovae, with no discernible contributions from Type Ia supernovae or asymptotic giant branch stars. The chemical and kinematic properties of HD 222925 suggest it formed in a low-mass dwarf galaxy, which was enriched by a high-yield r -process event before being disrupted by interaction with the Milky Way.

We derive dynamical parameters for a large sample of 446 r-process-enhanced (RPE) metal-poor stars in the halo and disk systems of the Milky Way, based on data releases from the R-Process Alliance, supplemented by additional literature samples. This sample represents more than a 10-fold increase in size relative to that previously considered by Roederer et al. and, by design, covers a larger range of r-process-element enrichment levels. We test a number of clustering analysis methods on the derived orbital energies and other dynamical parameters for this sample, ultimately deciding on application of the HDBSCAN algorithm, which obtains 30 individual chemodynamically tagged groups (CDTGs); 21 contain between 3 and 5 stars, and 9 contain between 6 and 12 stars. Even though the clustering was performed solely on the basis of their dynamical properties, the stars in these CDTGs exhibit statistically significant similarities in their metallicity ([Fe/H]), carbonicity ([C/Fe]), and neutron-capture element ratios ([Sr/Fe], [Ba/Fe], and [Eu/Fe]). These results demonstrate that the RPE stars in these CDTGs have likely experienced common chemical-evolution histories, presumably in their parent satellite galaxies or globular clusters, prior to being disrupted into the Milky Way’s halo. We also confirm the previous claim that the orbits of the RPE stars preferentially exhibit pericentric distances that are substantially lower than the present distances of surviving ultrafaint dwarf and canonical dwarf spheroidal galaxies, consistent with the disruption hypothesis. The derived dynamical parameters for several of our CDTGs indicate their association with previously known substructures, dynamically tagged groups, and RPE groups.