Analysis Of Clinical Efficacy And Safety Of Immune Checkpoint Inhibitors Plus Anti-angiogenic Agents In Common Malignant Tumors

Objective:We conducted this retrospective study to evaluate the effectiveness and safety of immune checkpoint inhibitors(ICIs)combined with anti-angiogenic agents(AAAs)in the treatment of common malignant tumors in our hospital,and the timing of combined treatment may be preliminarily explored.Methods:One hundred and sixty-nine patients with common malignant tumors who received ICIs combined with AAAs treatment in the Department of Oncology at Jiangxi Provincial People’s Hospital from August 2019 to April 2022 were selected as the research subjects.The first-line treatment regimen was defined as using ICIs or AAAs in the first-line treatment,followed by the combination of AAAs or ICIs,or both used simultaneously as first-line drugs.The second-line treatment regimen was defined as:ICIs combined with AAAs treatment was used in the second-line or post-second line treatment process,excluding ICIs or AAAs treatment used in the first-line treatment.Based on the approach of sequential treatment,they were divided into:immunotherapy cross-line group,anti-angiogenic targeted therapy cross-line group and combined treatment group.It is necessary to collect patients’clinical baseline data such as gender,age,smoking history,ECOG PS score,types of previous treatments received,types of ICIs and AAAs received,laboratory tests,adverse reactions and reasons for discontinuation of treatment;efficacy evaluation was performed according to RECIST1.1;ORR and DCR were calculated according to the formula;m PFS,1-year PFS rate,m OS and 1-year OS rate were obtained according to the Kaplan-Meier curve;adverse reactions were evaluated according to CTCAE5.0;results were analyzed using statistical software to evaluate the efficacy and safety of each regimen.Results:A total of 169 patients with malignant tumors who received ICIs combined with AAAs treatment were included.The main types of cancer were:lung cancer in 70 cases(41.42%),liver cancer in 51 cases(30.18%),and colorectal cancer in 22 cases(13.02%).29 patients(17.16%)received first-line ICIs combined with anti-angiogenic treatment and 140 patients(82.84%)received second-line treatment.The baseline data such as gender,age,ECOG score,and smoking history were comparable(P values all>0.05).At the same time,we selected the lung malignant tumor subgroup(n=70)for analysis,and the baseline data were also comparable(P values all>0.05).In terms of short-term efficacy(ORR and DCR),the overall ORR was 29.6%and the overall DCR was 82.8%.Among them:ORR(first-line treatment:second-line treatment)was 65.5%:22.1%,the difference was statistically significant(χ~2=21.69,P<0.001);DCR(first-line treatment:second-line treatment)was93.1%:80.7%,the difference was not statistically significant(χ~2=2.59,P=0.107);if the results were analyzed according to the type of cross-line treatment,there was no statistically significant difference among the three groups.In terms of long-term efficacy,the m PFS of common tumor types was 4.5 months and the 1-year PFS rate was 14.84%;the median overall survival m OS was 16.9 months and the 1-year OS rate was 67.06%.Among them,the m PFS(months)and 1-year PFS rate of lung subgroup were:first-line treatment was 10.0 and 40.27%,respectively;second-line treatment was 5.5 and 11.85%,respectively;the difference was statistically significant(χ~2=6.024,P=0.0141);liver m PFS(months)and 1-year PFS rate were:first-line treatment was 7.5 and 27.27%,respectively;second-line treatment was 3.0and 9.08%,respectively;the difference was statistically significant(χ~2=5.641,P=0.0175);m OS and 1-year OS rate were:first-line treatment was not reached and88.32%,respectively;second-line treatment was 16.9 and 64.55%,respectively;both differences were statistically significant(χ~2=6.682,P=0.0097).The more common adverse reactions were fatigue and loss of appetite;among them,ICI-related pneumonia,RCCEP,bone marrow suppression,hypoalbuminemia,nausea,rash,itching,immune myocarditis,fever and other adverse reactions did not show a statistically significant difference between the two groups.Conclusion:In the treatment of common malignant tumors,the use of ICIs or AAAs in first-line treatment has a statistically significant advantage over the addition of both in second-line treatment in terms of short-term efficacy(ORR)and long-term efficacy(m PFS,m OS,1-year PFS rate,and 1-year OS rate).The lung cancer subgroup and liver cancer subgroup showed the same trend,with no statistically significant difference in safety.Among them,in the cross-line treatment subgroup of lung malignant tumors(ICIs cross-line group,AAAs cross-line group and combined treatment group),there was no significant statistical difference between the three groups in terms of short-term efficacy and long-term efficacy.More clinical data is needed to support this.