The Impact Of Antibiotics On Efficacy Of Anti-PD-1 Therapy In Solid Tumors

Objective:We aim to investigate the relationship between the use of antibiotics and the efficacy of PD-1–based immunotherapy against advanced hepatocellular carcinoma and non-small cell lung cancer in Asian populations.Methods:1.The patients with advanced hepatocellular carcinoma(HCC)and non-small cell lung cancer(NSCLC)admitted between May 2016 and December 2017 in our cooperative hospitals,who have treated with anti-PD-1 antibody(Pembrolizumab/Nivolumab),with complete records of antibiotic use,treatment outcomes,adverse events and survival data,were studied retrospectively.2.The efficacy of the PD-1–based immunotherapy in advanced hepatocellular carcinoma and non-small cell lung cancer was evaluated according to Response Evaluation Criteria in Solid Tumors1.1(RECIST 1.1).And the adverse events were in accordance with the National cancer institute-common toxicity criteria adverse events version 4.0(NCI-CTCAE 4.0).3.Patients were divided into two groups according to whether they used antibiotics(use time ?3 days)during the time of 2 months before treatment and 1 month after treatment.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.And the factors influencing the prognosis were analysed by the univariate and multivariate survival analyses.4.Statistical analysis was performed by IBM SPSS software version 23.0.Results:1.A total of 61 patients were admitted to the study cohort,including 33 cases of advanced HCC patients treated with Nivolumab,11 cases of advanced NSCLC patients treated with Nivolumab and 17 cases of NSCLC patients treated with Pembrolizumb.During the treatment,none of the 61 patients had died of adverse drug reaction.The grade 1~2 adverse events had happened in 22 patients,including granulocytopenia and transaminase elevation.4 patients had experienced grade 3~4 toxic effects of elevated transaminases and pneumonia.During the time of 2 months before and 1 month after receiving anti-PD-1 antibody treatment,antibiotics were used mostly for pneumonia and infection in 14 patients with HCC and 13 patients with NSCLC.2.Among 33 patients with advanced HCC,there was no statistical difference in ORR(7.1% vs 10.5%,P=1.000),DCR(28.6% vs 57.9%,P=0.158),median PFS(2.0 months vs.3.7 months,P=0.293)and median OS(3.3 months vs.4.0 months,P = 0.757)between the antibiotic group and the non-antibiotic group.3.Among 28 patients with advanced NSCLC,there was no statistical difference in ORR(7.7% vs 13.3%,P=1.000)and DCR(38.5% vs 33.3%,P=1.000)between the antibiotic group and the non-antibiotic group.While there was significant statistical difference in median PFS(1.5 months vs.2.1 months,P = 0.046)and median OS(3.6 months vs.15.2 months,P = 0.014).The univariate analysis indicated that age and the use of antibiotics were significantly associated with overall survival.The multivariate analysis of the COX proportional hazards model confirmed that the use of antibiotics(P=0.029)was an independent factor that influenced the prognosis of NSCLC patients.4.Of all 61 patients,there was significant statistical difference in median PFS(1.8 months vs.2.8 months,P = 0.036)and median OS(3.6 months vs.4.8 months,P = 0.046).Conclusions:Antibiotics use can influence the response to anti-PD-1 immunotherapy in solid tumors in Asian populations.And antibiotics use may sever as a novel prognostic factors for PD-1–based immunotherapy.