Efficacy And Long-term Survival Outcomes Of Dose-dense Carboplatin Plus Paclitaxel As Neoadjuvant Chemotherapy For Triple-negative Breast Cancer

Objectives:To compare the efficacy of dose-dense(biweekly)carboplatin plus paclitaxel(PC)with standard 3-weekly PC as neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC),and to explore an optimal neoadjuvant chemotherapy regimen for TNBC.Methods:Patients with core needle biopsy confirmed pathological diagnosis of TNBC who received dose-dense PC(paclitaxel 175 mg/m2 d1,carboplatin AUC 4 d1,every 2 weeks)as NAC were 1:1 matched using propensity score matching(PSM)with TNBC patients who received standard 3-weekly PC(paclitaxel 175 mg/m2 d1,carboplatin AUC 5 d2,every 3 weeks).The primary endpoint was rate of pathologic complete response(pCR,ypT0/is ypN0).The secondary endpoint were objective response rate(ORR)、recurrence-free survival(RFS)、overall survival(OS)and safety.Results:Between January,2008 and September,2018,100 TNBC patients of stage IIAIIIC were enrolled(dose-dense group 50 patients,standard group 50 patients)with a median age of 47 years(range 24-75 years).65 patients were premenopausal.In dosedense group,49 patients completed 4-6 cycles of NAC,and 1 patient completed 3 cycles.In standard group,42 patients completed 4-6 cycles of NAC,and 8 patients completed 23 cycles.Of the 100 patients who were evaluated for clinical response,11 patients had complete response(CR),and 79 patients had partial response(PR),and the overall ORR was 90%.The ORR of dose-dense group and standard group were the same(90%).All patients underwent surgery after NAC and the overall pCR rate was 3 6%(36/100).The pCR rates were similar between the two groups:34%(17/50)in dose-dense group and 38%(19/50)in standard group,respectively(P=0.835).18 patients assessed BRCA1/2 mutation status,and 4 patients were BRCA1/2 mutation carriers,of which 2 patients had pCR.The most common adverse events were neutropenia.Due to the use of granulocyte colony stimulating factor(G-CSF),grade 3/4 neutropenia was less in dose-dense group than in standard group(32.7%vs.68.0%,P=0.001),while the rate of ALT/AST elevation was higher(57.1%vs.32.0%,P=0.015)in dose-dense group.The median follow-up time was 55 months(3～150 months).In overall population,5-year RFS was 77.3%.5-year RFS was non-significantly higher in dose-dense group than in standard group(83.5%vs.75.2%,P=0.809).5-year OS was 85.7%in overall population,and similar in dose-dense and standard group(87.9%vs.84.5%,P=0.624).Patients who achieved pCR after NAC had significantly better 5-year RFS(90.7%vs.69%,P=0.032)and 5-year OS(100%vs.76.9%,P=0.002)than patients with residual disease.Conclusions:Dose-dense PC had similar efficacy with standard 3-weekly PC and had a good safety profile.Since dose-dense regimen could shorten the duration of therapy,it could be an alternative in TNBC.