Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy

BACKGROUND: This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). METHODS: Eligible women had progressed on (neo)adjuvant endocrine therapy (ET),  ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety. RESULTS: In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380-1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390-1.463). CONCLUSIONS: Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population. CLINICAL TRIAL REGISTRATION: NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703

Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory

AbstractH5N1 highly pathogenic avian influenza (HPAI) viruses were isolated from dead wild waterfowl at Khunt, Erkhel, Doityn Tsagaan, Doroo, and Ganga Lakes in Mongolia in July 2005, May 2006, May 2009, July 2009, and May 2010, respectively. The isolates in 2005 and 2006 were classified into genetic clade 2.2, and those in 2009 and 2010 into clade 2.3.2. A/whooper swan/Mongolia/6/2009 (H5N1) experimentally infected ducks and replicated systemically with higher mortality than that of the isolates in 2005 and 2006. Intensive surveillance of avian influenza in migratory waterfowl flying from their nesting lakes in Siberia to Mongolia in every autumn indicate that HPAI viruses have not perpetuated at their nesting lakes until 2009. The present results demonstrate that wild waterfowl were sporadically infected with H5N1 HPAI viruses prevailing in domestic poultry in the southern Asia and died in Mongolia on the way back to their northern territory in spring

Plant Nitrogen Levels and Photosynthesis in the Supernodulating (Glycine max L. Merr.) Cultivar ‘Sakukei 4’

Supernodulating soybeans, having several times more nodules than normal genotypes, are expected to produce higher dry matter and grain yields through a higher nitrogen fixation potential. However, their growth and yield have been inferior to those of normal genotypes. We have recently developed the supernodulating genotype‘Sakukei 4’(formerly‘En-b0-1-2’, presently‘Kanto 100’), with improved growth and yield and a high nitrogen fixation potential. The objective of the present study was to examine the time course of changes in plant nitrogen content, leaf chlorophyll content (SPAD value), and photosynthetic rate of Sakukei 4 to reveal the source of its advantages in growth. The leaf nitrogen content after the flowering stage and the stem nitrogen content after the seed-filling stage were higher in Sakukei 4 than in the normal cultivar‘Enrei’. The SPAD values in Enrei and another normal cultivar,‘Tamahomare’, decreased rapidly after the seed-filling stage, whereas that in Sakukei 4 stayed high until the late seed-filling stage. Differences in photosynthetic rate and leaf SPAD value between Sakukei 4 and Enrei were negligible at the beginning of podding but became very clear at the seed-filling stage because of the drop in the values for Enrei. In Sakukei 4, a large amount of nitrogen might not be translocated from leaf to seed during the seed-filling stage because of the higher capability of the nodules to send fixed nitrogen to the growing seeds. Sakukei 4 could thus maintain a high photosynthetic rate and grain growth during the seed-filling stage

Characteristics of Nodulation and Nitrogen Fixation in the Improved Supernodulating Soybean (Glycine max L. Merr.) Cultivar ‘Sakukei 4’

Supernodulating soybean lines have more than several times as many nodules as normal cultivars. They are expected to have high nitrogen-fixing ability and enhanced productivity, but their yields have been inferior to those of normal genotypes. We have recently developed a new supernodulating cultivar,‘Sakukei 4’(formerly ‘En-b0-1-2’, presently‘Kanto 100’), with improved growth and yield. The objective of the present study was to identify the characteristics of the nodulation and nitrogen-fixing ability of Sakukei 4. In pot trials, the nodule number of Sakukei 4 was 8.3 times that of a normal cultivar,‘Enrei’, and the nodule weight per plant was 2.3 to 2.8 times the value for Enrei. The acetylene reduction activity per plant in Sakukei 4 was higher than that in Enrei and conventional supernodulating genotypes, especially during the late growth stage. Compared with conventional supernodulating lines, the improved vegetative growth in shoots and roots of Sakukei 4, especially after flowering, probably enhanced its nitrogen-fixing ability per plant. We consider that its high nitrogen-fixing ability at the seed-filling stage, would help increase its yield in fields with low nitrogen fertility

Characteristics of Growth and Yield Formation in the Improved Genotype of Supernodulating Soybean (Glycine maxL. Merr.)

Most of the supernodulating soybean lines were agronomically inferior to conventional genotypes. Our previous tests with ‘En6500’, a supernodulating mutant derived from a variety ‘Enrei’, revealed that its low growth and yield were not necessarily due to supernodulation. In our attempts to improve the yield of En6500 through crossing with Enrei, we recently succeeded in selecting a supernodulating line showing vigorous growth. Field experiments with this new supernodulating line ‘En-bO-1-2’ for three years revealed that it yielded much more than En6500. When the overall yield level was low, it even tended to yield more than Enrei. En-bO-1-2 thus showed a remarkably higher productivity than other supernodulating lines reported so far. Its improved yield was largely due to : (a) better seed filling, (b) vigorous vegetative growth during flowering period, and (c) high leaf area index and leaf N content that enabled production of more photosynthates to enhance N fixation and dry matter accumulation during the period of pod and seed development