Background:The standard first-line treatment for human epidermal growth factor receptor 2(HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel.This study aimed...Background:The standard first-line treatment for human epidermal growth factor receptor 2(HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel.This study aimed to evaluate the effectiveness of KN026,an anti-HER2 bispecific antibody,plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer.Methods:This open-label,single-arm,phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30,2019 to May 27,2021.Patients were administered KN026(30 mg/kg)plus docetaxel(75 mg/m2)in 21-day cycles.Primary endpoints included the objective response rate(ORR)and duration of response(DOR).In addition,overall survival(OS),progression-free survival(PFS),clinical benefit rate(CBR)and safety profile were examined.Results:A total of 57 patients were included.In the efficacy analysis set of 55 patients,the ORR was 76.4%(95%confidence interval[CI],63.0%-86.8%),and the CBR was 85.5%(95%CI,73.3%-93.5%).The median DOR was not reached(95%CI,20.7 months-not reached).In the safety set of 57 patients,the median PFS was 27.7 months(95%CI,18.0 months-not reached).The median OS was not reached,with OS rates at 12,24 and 30 months of 93.0%,84.1%and 78.5%,respectively.Grade≥3 treatment-emergent adverse events(AEs)were detected in 36(63.2%)patients.No deaths were attributed to KN026 or docetaxel.Conclusion:KN026 plus docetaxel showed promising efficacy and a manageable safety profile in first-line treatment of HER2-positive recurrent/metastatic breast cancer.展开更多
●15 years cattle manure addition enhanced soil P availability and lettuce yield.●gcd and phoD gene abundances increased under manure treatments,correlating with available P.●Combined manure and chemical fertilizers...●15 years cattle manure addition enhanced soil P availability and lettuce yield.●gcd and phoD gene abundances increased under manure treatments,correlating with available P.●Combined manure and chemical fertilizers led to increased microbial community diversity.●Positive interactions within microbial networks were higher in manure-applied soils.●Key microbial taxa were identified as crucial drivers of P transformation.Long-term cattle manure application significantly influences soil phosphorus(P)cycling and associated microbial communities in agricultural systems.However,the mechanisms by which Ptransforming microbial communities and their ecological networks mediate P cycling and crop productivity under sustained organic amendment remain poorly understood.This study investigated the effects of 15-year cattle manure application on soil P forms,P-solubilizing microbial communities,and lettuce(Lactuca sativa)yields across three treatments:no fertilization(control),manure-only(M),and combined manure and chemical fertilizer(M+CF).The M+CF treatment significantly enhanced lettuce yields by 77%compared to control and 41%compared to M treatment,while increasing P content by 3.9%and 2.1%,respectively.Metagenomic analysis revealed that manure application increased the diversity(Shannon index:+32.5%)and abundance(+260%)of phoD-harboring bacteria in the M treatment,while M+CF enhanced both diversity(+45.3%)and abundance(+290%)of gcd-harboring bacteria.Proteobacteria(54.2%−68.8%),Acidobacteria(24.2%−33.2%),and Gemmatimonadetes dominated the P-solubilizing bacterial communities across treatments.Network analysis demonstrated that M+CF treatment increased positive microbial correlations by 74.6%compared to control,with enhanced connectivity among keystone taxa,particularly for gcd-harboring microorganisms.Soil enzyme activities showed strong correlations with gene abundances(R^(2)=0.92 for gcd-ACP;R^(2)=0.86 for phoD-ALP),suggesting functional linkages between microbial community composition and P transformation processes.Overall,these findings demonstrate that appropriate long-term fertilization strategies can optimize soil P use efficiency,enhance microbial-mediated P transformations,and improve vegetable yields,providing insights for sustainable nutrient management in intensive cropping systems.展开更多
文摘Background:The standard first-line treatment for human epidermal growth factor receptor 2(HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel.This study aimed to evaluate the effectiveness of KN026,an anti-HER2 bispecific antibody,plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer.Methods:This open-label,single-arm,phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30,2019 to May 27,2021.Patients were administered KN026(30 mg/kg)plus docetaxel(75 mg/m2)in 21-day cycles.Primary endpoints included the objective response rate(ORR)and duration of response(DOR).In addition,overall survival(OS),progression-free survival(PFS),clinical benefit rate(CBR)and safety profile were examined.Results:A total of 57 patients were included.In the efficacy analysis set of 55 patients,the ORR was 76.4%(95%confidence interval[CI],63.0%-86.8%),and the CBR was 85.5%(95%CI,73.3%-93.5%).The median DOR was not reached(95%CI,20.7 months-not reached).In the safety set of 57 patients,the median PFS was 27.7 months(95%CI,18.0 months-not reached).The median OS was not reached,with OS rates at 12,24 and 30 months of 93.0%,84.1%and 78.5%,respectively.Grade≥3 treatment-emergent adverse events(AEs)were detected in 36(63.2%)patients.No deaths were attributed to KN026 or docetaxel.Conclusion:KN026 plus docetaxel showed promising efficacy and a manageable safety profile in first-line treatment of HER2-positive recurrent/metastatic breast cancer.
基金supported by the National Key R&D program Project(Grant No.2022YFD1901504-06)Talent program of Yunnan Province(Grant No.202405AC350095)+1 种基金Farmland non-point source prevention and control innovation team of Yunnan Province(Grant No.202405AS350023)Joint Fund for Agriculture of Yunnan Province(Grant No.202301BD070001-046).
文摘●15 years cattle manure addition enhanced soil P availability and lettuce yield.●gcd and phoD gene abundances increased under manure treatments,correlating with available P.●Combined manure and chemical fertilizers led to increased microbial community diversity.●Positive interactions within microbial networks were higher in manure-applied soils.●Key microbial taxa were identified as crucial drivers of P transformation.Long-term cattle manure application significantly influences soil phosphorus(P)cycling and associated microbial communities in agricultural systems.However,the mechanisms by which Ptransforming microbial communities and their ecological networks mediate P cycling and crop productivity under sustained organic amendment remain poorly understood.This study investigated the effects of 15-year cattle manure application on soil P forms,P-solubilizing microbial communities,and lettuce(Lactuca sativa)yields across three treatments:no fertilization(control),manure-only(M),and combined manure and chemical fertilizer(M+CF).The M+CF treatment significantly enhanced lettuce yields by 77%compared to control and 41%compared to M treatment,while increasing P content by 3.9%and 2.1%,respectively.Metagenomic analysis revealed that manure application increased the diversity(Shannon index:+32.5%)and abundance(+260%)of phoD-harboring bacteria in the M treatment,while M+CF enhanced both diversity(+45.3%)and abundance(+290%)of gcd-harboring bacteria.Proteobacteria(54.2%−68.8%),Acidobacteria(24.2%−33.2%),and Gemmatimonadetes dominated the P-solubilizing bacterial communities across treatments.Network analysis demonstrated that M+CF treatment increased positive microbial correlations by 74.6%compared to control,with enhanced connectivity among keystone taxa,particularly for gcd-harboring microorganisms.Soil enzyme activities showed strong correlations with gene abundances(R^(2)=0.92 for gcd-ACP;R^(2)=0.86 for phoD-ALP),suggesting functional linkages between microbial community composition and P transformation processes.Overall,these findings demonstrate that appropriate long-term fertilization strategies can optimize soil P use efficiency,enhance microbial-mediated P transformations,and improve vegetable yields,providing insights for sustainable nutrient management in intensive cropping systems.
