Clinical Observation Of Effect And Adverse Reaction Of PD-1 Inhibitor On Advanced Tumor Patients

Object:Immunotherapy at immune checkpoints has become an important component of the treatment patterns of many malignancies,especially PD1/PD-L1 blockade,which has been shown to rejuvenate inactivated T cells in cancer patients for long-term remission.A number of clinical studies have shown that PD1 antibodies have achieved good trial results in the treatment of malignant melanoma,non-small cell lung cancer,bladder cancer,renal cancer,breast cancer,ovarian cancer and other malignant tumors Thanti-mab Nivolumab and Pembrolizumab,approved by FDA have been listed in China for the treatment of malignant melanoma,lung cancer and so on.this study retrospectively analyzed the clinical data of 57 patients treated with advanced tumors by pdl inhibitors(Nivolumab/Pembrolizumab)to evaluate their clinical efficacy,progression-free survival and safety,and to provide a basis for the application of immunotherapy in advanced tumorsMethod:From May 1,2017 to January 15,2020,A collection of 57 patients with multiple advanced malignancies,including 23 with Nivolumab and 34 with Pembrolizumab,were seen in the first affiliated hospital of dalian University.RECIST 1.1 and NCI-CTC 4.0 were used to evaluate the short-term efficacy and adverse reactions of 57 patients,respectively.Subjects were followed up by a combination of hospitalization and telephone follow-up by the first affiliated hospital of dalian medical university,where patients were followed up to the progression and death of the disease.Or stop treatment due to unbearable adverse reactions,or the 15 th january 2020 deadline.the primary analytical endpoints were disease control rate,objective response rate,secondary end point was progression-free survival and toxicity.Result:57 patients until the end of follow-up,2 can not evaluate the efficacy.Of the 32 patients using Pembrolizumab inhibitor,PR 7 cases(21.9%),SD 19 cases(59.4%)and PD6 cases(18.8%),but none of them reached the CR.the DCR was 81.2%(26/32)and the ORR was 21.9%(7/32);the non-small cell lung cancer subgroup DCR was 93.8%(15/16)and the ORR was 43.8%(7/16);the median PFS was 11.23 months(95%).12 patients still continued immunotherapy without progress,8 patients(25.0%)died and 24 patients(75.0%)are still alive.PR 2 cases(8.7%),SD 16 cases(69.6%)and PD5 cases(21.7%)of the 23 patients treated with Nivolumab,but none of them reached the CR.DCR was 78.3%(18/23)and ORR was 8.7%(7/23);subgroup DCR of non-small cell lung cancer was 100%(7/7)and ORR was 14.3%(1/7);median PFS was 8.80 months(95%).8 patients still continued immunotherapy without progress,4(17.4%)patients died and 19(82.6%)patients are still alive.Univariate analysis of Pembrolizumab showed PFS and PD-L1 TPS<1%,?1%<50%and?50%was statistically significant(P=0.001).Univariate analysis showed no significant difference between PFS and clinical stage(P=0.294),age(P=0.923),sex(P=0.978),smoking(P=0.652),ECOG score(P=0.107),brain metastases(P=0.628),single anti-first-line second-line treatment or third-line treatment and above(P=0.766),single-drug or combination therapy(P=0.797),TMB<10 and TMB?10(0.741).On the single factor analysis showed that single PFS about Nivolumab with ECOG score was statistically significant(P=0.004),Univariate analysis showed no significant difference between PFS and clinical stage(P=0.975),age(P=0.061),gender(P=0.635),smoking(P=0.529),brain metastases(P=0.986),single anti-first-line second-line treatment or third-line treatment and above(P=0.882),single or combination therapy(P=0.573),the PD-L1 TPS<1%;TMB<10 and TMB?10(0.123).About lung cancer,ORR was 0/3(0%)in PD-L1 TPS<1%.and 0/7(0%)in?1%,<50%and 2/9(22.2%)in?50%;which was statistically significant differences between groups(p<0.001)57 patients received PD1 monotherapy,of which 23 were treated with nivolumab and 34 with pembrolizumab.At the end of the follow-up,the median PFS was 8.90 months(95%CI:6.621-11.179)and the median OS was 12.76 months(95%CI:12.0683.452).lung cancer subgroups had a median PFS of 10.73 months(95%CI:8.431-13.029)and median OS of 13.07 months(95%CI:12.421-13.719).Five patients were stopped because of adverse reactions,and 20 patients continued immunotherapy without progress.Twelve patients(21.1%)died and 45(78.9%)are still aliveConclusion:1.The results of this study show that PD1 antibody(Nivolumab/Pembrolizumab)is effective,tolerable and controllable in the treatment of advanced malignant tumors2.Nivolumab and Pembrolizumab disease control rates are similar,and the median PFS of the Pembrolizumab group is slightly longer than that of the Nivolumab group Considering the current low number of cases,bias and other confounding factors,more large clinical trial studies are needed3.Nivolumab and Pembrolizumab were different,the incidence of adverse reactions in Pembrolizumab group was higher than that in Nivolumab group,but the incidence of adverse reactions in grade 3 and 4 was low,and there was no significant difference in the data4.Univariate analysis of Pembrolizumab antibody showed that the expression of PFS and PD-L1 TPS was statistically significant,but not statistically different from the TMB size.Univariate analysis of the Nivolumab antibody group showed that the size of PFS and PD-L1 TPS was not statistically significant,as was TMB.Therefore,in Pembrolizumab antibody,PD-L1 TPS is more instructive as curative effect predictor,and in Nivolumab antibody,TMB curative effect predictor is more instructive.From this study found that this problem deserves further exploration,and this conclusion still needs to be further verified by large sample clinical trials5.In lung cancer,the higher the expression of PD-L1 TPS,the better the curative effect.