Efficacy And Safety Of PD-1/PD-L1 Inhibitors Plus Chemotherapy For Triple Negative Breast Cancer:A Systematic Review And Meta-analysis

Background: To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy compared with chemotherapy in the treatment of triple negative breast cancer。Methods: Relevant articles were sought in PubMed,EMBASE,Cochrane Library and Web of Science,CBM,CNKI and Wanfang database and abstracts of major international conferences。Possible eligible tests were determined。The end point of our study were the rate of pathological complete response(PCR),overall survival(OS),progress free survival(PFS),disease free survival(DFS),and the incidence of adverse events(any grade).According to the heterogeneity between the studies,the relative risk(RR)、hazard ratio(HR)and 95% confidence interval(CI)of each point were calculated by using fixed or random effect model.Revman 5.3 and Stata 12.0 software were used for meta-analysis.Results: This study included 7 RCTs with a total of 4,566 patients。Pooled results showed that PD-1/PD-L1 inhibitors plus neoadjuvant chemotherapy(NACT)significantly improved the p CR rate(RR=1.33 95%CI[1.19-1.48],P<0.001)and DFS rate(HR=0.66,95% CI [0.48,0.92]P=0.015)in TNBC patients.Among patients with advanced stage,anti-PD-1/PD-L1 therapy plus chemotherapy also significantly improved the PFS rate(HR for progression or death 0.82,95% CI[0.74,0.90],P<0.001)but OS rate could not benefit from the combined therapy(HR for death 0.93,95% CI[0.82,1.06] P=0.289).In terms of safety,adverse events(grade 3 or more)were more common in PD-1/PD-L1 inhibitors plus chemotherapy group(RR=1.1,95% CI[1.05,1.16]P<0.001).Adverse events(any grade)included the hyperthyroidism and hypothyroidism,were more common in the combined group(RR=5.05,95% CI [2.55-9.97] P<0.001,RR=4.19 95% CI [3.06-5.74] P<0.001),except them,there is no difference in other adverse reactions.Conclusions:(1)PD-1/PD-L1 inhibitors combined with chemotherapy in neoadjuvant therapy can increase the p CR rate and DFS rate in patients with triple-negative breast cancer.(2)PD-1/PD-L1 inhibitors combined with chemotherapy cannot improve the OS rates in patients with advanced triple-negative breast cancer(3)PD-1/PD-L1 inhibitors plus chemotherapy have significantly higher incidence of adverse events(AEs)of grade 3 or higher.The safety profile are acceptable.