Background:The ASTRUM-005 study previously demonstrated a signifi-cant overall survival(OS)benefit with serplulimab(a programmed death1 inhibitor)plus chemotherapy versus chemotherapy alone in previouslyuntreated exte...Background:The ASTRUM-005 study previously demonstrated a signifi-cant overall survival(OS)benefit with serplulimab(a programmed death1 inhibitor)plus chemotherapy versus chemotherapy alone in previouslyuntreated extensive-stage small-cell lung cancer(ES-SCLC).Here,we reportupdated efficacy and safety results after an extended median follow-up of 19.8months,along with the first report on findings from exploratory biomarkeranalyses.Methods:A total of 585 patients were randomized in a 2:1 ratio to receive4.5 mg/kg serplulimab(n=389)or placebo(n=196)intravenously every 3weeks,together with carboplatin and etoposide.The primary endpoint was OS.In addition,genomic profiling was performed to identify mutated genes,and quantitative serum proteome profiling was conducted to identify differ-entially expressed proteins(DEPs)between responders and non-responders ofserplulimab plus chemotherapy.Regression analysis was subsequently used toconstruct a protein signature based on the DEPs.The associations betweenefficacy outcomes(objective response rate[ORR],OS,and progression-free sur-vival[PFS])and gene mutation status or DEP expression were also examinedwith regression analysis.Furthermore,the prognostic value of hematologicalparameters was evaluated.Results:In the intent-to-treat population,the median OS was 15.8 monthsin the serplulimab group versus 11.1 months in the placebo group(haz-ard ratio,0.62;95%confidence interval,0.50-0.76;P<0.001).We identified181 DEPs between responders and non-responders in the serplulimab group,from which a 15-protein signature was constructed.In the serplulimab group,patients with a higher 15-protein signature score were associated with sig-nificantly longer OS and PFS.Also,patients harboring tumor-suppressorretinoblastoma-1(RB1)mutations or mutations in Notch pathway membersshowed improved ORR,OS,or PFS compared with their wild-type counter-parts.Baseline neutrophil-to-lymphocyte ratio(NLR)and lactate dehydrogenase(LDH)level were independent prognosticators of patients with ES-SCLC.Conclusions:First-line serplulimab provided a sustained clinical benefit overplacebo in patients with ES-SCLC.A 15-protein signature and mutations in RB1or Notch pathway genes may serve as predictive biomarkers for benefits fromserplulimab plus chemotherapy,while baseline NLR and LDH were independentprognosticators for ES-SCLC.展开更多
With wide applications of electromagnetic instruments and equipments in medical treatment, scientific re- search and national defense, and daily life items of computers, mobile telephones, and microwave ovens etc, ele...With wide applications of electromagnetic instruments and equipments in medical treatment, scientific re- search and national defense, and daily life items of computers, mobile telephones, and microwave ovens etc, elec- tromagnetic radiations have brought us great benefit. However, there are potential damages with electromagnetic radiations,e.g. the electromagnetic pulse (EMP), which is not ionizing radiation but can cause vibration of atoms or molecules and alter electron energy levels. It has been reported that EMP could decrease the learning and recol- lection ability of mice and rats through inducing metabolic disorder of neurotransmitter in mice brain and affect the brain wave of anesthetized rats. EMP also has some effect on immune, procreation and endocrine system of mice. The integrity of the blood-brain barrier (BBB) was detected in order to observe the effects of J005A electro- magnetic wave shielding textile (JEWST) on bio-effects of EMP. 48 BALB/c male mice were randomly divided into exposure groups and JEWST protection groups (n=6). EMP was generated from a bounded-wave simulator and transmitted into a GTEM cell in which the mice were exposed. The field intensity was 0, 100, 200 and 400 kV m-1, respectively. The integrity of the BBB was determined by a quantitative measurement of Evans blue (EB) dye. The quantity of penetrated EB in brains of the mice increased obviously after exposure to 100, 200and 400 kV m-1 EMP, compared with the control groups (p<0.0 1). In JEWST prevention groups, the quantity of penetrated EB was significantly decreased after exposure compared with the exposure groups. EMPs of 100, 200 and 400 kV m-1 could increase the permeability of BBB in mice. The J005A electromagnetic wave shieldlng textile may prevent BBB from EMP induced BBB injury in mice.展开更多
基金Shanghai Henlius Biotech Inc.NationalNatural Science Foundation of China,Grant/Award Number:82473000。
文摘Background:The ASTRUM-005 study previously demonstrated a signifi-cant overall survival(OS)benefit with serplulimab(a programmed death1 inhibitor)plus chemotherapy versus chemotherapy alone in previouslyuntreated extensive-stage small-cell lung cancer(ES-SCLC).Here,we reportupdated efficacy and safety results after an extended median follow-up of 19.8months,along with the first report on findings from exploratory biomarkeranalyses.Methods:A total of 585 patients were randomized in a 2:1 ratio to receive4.5 mg/kg serplulimab(n=389)or placebo(n=196)intravenously every 3weeks,together with carboplatin and etoposide.The primary endpoint was OS.In addition,genomic profiling was performed to identify mutated genes,and quantitative serum proteome profiling was conducted to identify differ-entially expressed proteins(DEPs)between responders and non-responders ofserplulimab plus chemotherapy.Regression analysis was subsequently used toconstruct a protein signature based on the DEPs.The associations betweenefficacy outcomes(objective response rate[ORR],OS,and progression-free sur-vival[PFS])and gene mutation status or DEP expression were also examinedwith regression analysis.Furthermore,the prognostic value of hematologicalparameters was evaluated.Results:In the intent-to-treat population,the median OS was 15.8 monthsin the serplulimab group versus 11.1 months in the placebo group(haz-ard ratio,0.62;95%confidence interval,0.50-0.76;P<0.001).We identified181 DEPs between responders and non-responders in the serplulimab group,from which a 15-protein signature was constructed.In the serplulimab group,patients with a higher 15-protein signature score were associated with sig-nificantly longer OS and PFS.Also,patients harboring tumor-suppressorretinoblastoma-1(RB1)mutations or mutations in Notch pathway membersshowed improved ORR,OS,or PFS compared with their wild-type counter-parts.Baseline neutrophil-to-lymphocyte ratio(NLR)and lactate dehydrogenase(LDH)level were independent prognosticators of patients with ES-SCLC.Conclusions:First-line serplulimab provided a sustained clinical benefit overplacebo in patients with ES-SCLC.A 15-protein signature and mutations in RB1or Notch pathway genes may serve as predictive biomarkers for benefits fromserplulimab plus chemotherapy,while baseline NLR and LDH were independentprognosticators for ES-SCLC.
文摘With wide applications of electromagnetic instruments and equipments in medical treatment, scientific re- search and national defense, and daily life items of computers, mobile telephones, and microwave ovens etc, elec- tromagnetic radiations have brought us great benefit. However, there are potential damages with electromagnetic radiations,e.g. the electromagnetic pulse (EMP), which is not ionizing radiation but can cause vibration of atoms or molecules and alter electron energy levels. It has been reported that EMP could decrease the learning and recol- lection ability of mice and rats through inducing metabolic disorder of neurotransmitter in mice brain and affect the brain wave of anesthetized rats. EMP also has some effect on immune, procreation and endocrine system of mice. The integrity of the blood-brain barrier (BBB) was detected in order to observe the effects of J005A electro- magnetic wave shielding textile (JEWST) on bio-effects of EMP. 48 BALB/c male mice were randomly divided into exposure groups and JEWST protection groups (n=6). EMP was generated from a bounded-wave simulator and transmitted into a GTEM cell in which the mice were exposed. The field intensity was 0, 100, 200 and 400 kV m-1, respectively. The integrity of the BBB was determined by a quantitative measurement of Evans blue (EB) dye. The quantity of penetrated EB in brains of the mice increased obviously after exposure to 100, 200and 400 kV m-1 EMP, compared with the control groups (p<0.0 1). In JEWST prevention groups, the quantity of penetrated EB was significantly decreased after exposure compared with the exposure groups. EMPs of 100, 200 and 400 kV m-1 could increase the permeability of BBB in mice. The J005A electromagnetic wave shieldlng textile may prevent BBB from EMP induced BBB injury in mice.
