Platinum is essential in neoadjuvant treatment of triple-negative breast cancer: a network meta-analysis

Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochrane Library,and Web of Science were searched in May 2020 to identify randomized controlled trials(RCTs).Bayesian network meta-analysis(NMA)was performed(Registration:PROSPERO CRD42020223012).Results:A total of 35 RCTs involving 8,424 participants were reviewed,of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response(pCR).An anthracycline-taxane-based(AT)regimen combined with a platinum(ATPt)[odds ratio(OR)=2.04,95%credible interval(CrI):1.69,2.48]regimen,and a docetaxel regimen combined with a carboplatin(TCb;OR=2.16,95%CrI:1.20,3.91)regimen improved pCR beyond that with AT only.AT and ATPt combined with targeted therapy[including bevacizumab(Bev),veliparib,atezolizumab,or pembrolizumab]also improved pCR.Five RCTs included in this NMA reported serious adverse events(SAEs)or grade≥3 AEs.TCb was associated with fewer grade≥3 AEs than was AT(OR=0.66,95%CrI:0.23,1.72)alone.In contrast,ATPt,AT+Bev,ATPt+Bev,ATPt+veliparib,and ATPt+pembrolizumab were associated with more SAEs than was AT alone.Conclusions:In patients with TNBC,platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone,but TCb appears to be better tolerated than either AT or ATPt.Platinum-based regimens combined with targeted therapies(Bev,PARPi,and PD-1/PD-L1 inhibitor)also improve the pCR rate beyond that with AT alone,but this benefit is accompanied by greater toxicity.

Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease:baseline data and statistical analysis plan for the Lacunar Intervention Trial-2(LACI-2)(ISRCTN14911850)

Background Cerebral small vessel disease(SVD)causes lacunar strokes(25%of all ischaemic strokes),physical frailty and cognitive impairment and vascular and mixed dementia.There is no specific treatment to prevent progression of SVD.Methods The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression.We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol,isosorbide mononitrate,both or neither,in addition to guideline secondary ischaemic stroke prevention,in a partial factorial design.The primary outcome is feasibility of recruitment and adherence to medication;key secondary outcomes include:drug tolerability;recurrent vascular events,cognition and function at 1 year after randomisation;and safety(bleeding,falls,death).Data are number(%)and median(IQR).Results The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised,with the following baseline characteristics:average age 64(56.0,72.0)years,female 112(30.9%),stroke onset to randomisation 79.0(27.0,244.0)days,hypertension 267(73.6%),median blood pressures 143.0(130.0,157.0)/83.0(75.0,90.0)mm Hg,current smokers 67(18.5%),educationally achieved end of school examinations(A-level)or higher 118(32.5%),modified Rankin scale 1.0(0.0,1.0),National Institutes Health stroke scale 1.0(1.4),Montreal Cognitive Assessment 26.0(23.0,28.0)and total SVD score on brain imaging 1.0(0.0,2.0).This publication summarises the baseline data and presents the statistical analysis plan.Summary The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.Trial registration number ISRCTN14911850.