| Purpose To analyze the efficacy and safety of PD-1 inhibitors combined with different chemotherapy regimens in patients with advanced gastric cancer by retrospective analysis.and expound the relationship between the combination therapy strategy and related proteins by referring pathological indicators.Methods In this paper,102 cases of late stage gastric cancer in Subei People’s Hospital were analyzed retrospectively between Jan 2020 and Aug.2022,and at least one metastasis was evaluable.All patients in the group received the treatment strategy of immune checkpoint inhibitors combined with different chemotherapy regimens,and were followed up until tumor progression or serious adverse drug reactions occurred and treatment was stopped or death occurred.According to the treatment plan that the patients actually received,the patients were divided into PD-1 inhibitors combined with paclitaxel drugs group(48 cases)and PD-1 inhibitors combined with non-paclitaxel drugs group(54 cases);According to the different PD-1 inhibitors received,they were divided into three groups: 52 cases in the Sintilimab group,26 cases in the Camrelizumab group,and 24 cases in the Tislelizumab group;The patients were divided into liver metastasis group(47 cases)and other site metastasis group(55 cases)according to whether they had liver metastasis;According to whether the age of patients is more than 70 years old,they are divided into 31 patients over 70 years old and 71 patients under 70 years old.The reference standards for efficacy and safety evaluation were immune Response Evaluation Criteria in Solid Tumors version(iRECIST),with two treatment cycles,respectively.The primary end points included overall survival(OS)and progression-free survival(PFS),and the secondary end points included objective response rate(ORR),disease control rate(DCR)and safety.The expression of EGFR、P53、Ki67、GST-π、ERCC1 and Pgp in the pathological samples of 32 patients was statistically analyzed to explore the correlation between the expression level of target protein and the combined treatment strategy.Results 1.In terms of short-term curative effect,the median progression-free survival(mPFS)and median overall survival(mOS)of 102 patients were 9.3 months and 15.2months,respectively,as of August 30,2022.There were 0 cases of immune complete response(iCR),68 cases of immune partial response(iPR),19 cases of immune stable disease(iSD),15 cases of immune confirmed progressive disease(i CPD),with ORR of66.67% and DCR of 85.29%.2.Efficacy analysis of paclitaxel group and non-paclitaxel group: The mPFS of paclitaxel group and non-paclitaxel group were 11.3 months and 9.2 months respectively(P=0.034),the difference was statistically significant;the mOS was 18.1months and 13.2 months respectively(P=0.026),the difference was statistically significant.There were 35 and 33 iPR in the paclitaxel group and the non-paclitaxel group,respectively,the ORR of the two groups was 72.92% and 61.11%(P=0.293),the DCR was 89.58% and 81.48%,respectively(P=0.383),with no statistical difference.3.To compare the effect of combination with different PD-1 inhibitors on the survival period of patients: The mPFS of Sintilimab group,Camrelizumab group and Tislelizumab group were 8.2 months,10 months and 11.3 months respectively(P=0.392),with no statistical difference;the mOS was 14.1 months,12.1 months and not reached,respectively(P=0.267),with no statistical difference.The ORR of the three groups was 63.46%,65.38%,75%(P=0.604),with no statistical difference,while the DCR was 80.77%,88.46%,91.67%(P=0.40),with no statistical difference.4.The effect of liver metastasis on the PD-1 combination therapy: The mPFS of liver metastasis group and other site metastasis group was 10.0 months and 9.2 months(P=0.490);the mOS was 16.4 months and 13.2 months(P=0.442),the ORR of the two groups was 61.70% and 70.91%,respectively(P=0.444),the DCR was 85.11% and85.45%,respectively(P=0.590),the difference was not statistically significant.5.The effect of chemotherapy combined with immunotherapy on the survival period of patients beyond 70 years old: The mPFS of patients beyond 70 years old and patients under 70 years old were 8.4 months and 9.3 months,respectively(P=0.040),with statistical difference;the mOS was 13.2 months and 15.2 months respectively(P=0.310),with no statistical difference.The ORR of the two groups was 67.74% and 66.20%,respectively(P=0.818),and the DCR was 83.87% and 85.91%,respectively(P=0.628),the difference was not statistically significant.6.Relationship between the expression level of tissue protein and combined treatment strategy: Univariate analysis showed that P53 and ERCC1 were significantly correlated with the efficacy of combined therapy for advanced gastric cancer(P53: HR=0.158;95% CI: 0.034-0.738,P=0.019);(ERCC1: HR=5.44;95%CI: 1.429-20.746,P=0.013).Multivariate analysis showed that P53 and ERCC1 were independent risk factors for OS in the immunotherapy of advanced gastric cancer(P53: HR=0.159;95% CI:0.032-0.783,P=0.024);(ERCC1: HR=4.47;95%CI: 1.096-18.233,P=0.037),the difference was statistically significant.Conclusions 1.Retrospective studies have shown that immune checkpoint inhibitors combined with chemotherapy has longer mPFS and mOS than chemotherapy alone(historical data)in the first-line treatment of advanced gastric cancer,which further conforms to the current standard for first-line treatment of advanced gastric cancer.2.In terms of the exact drugs selection of immunotherapy combined with chemotherapy,the retrospective study showed that the combination of paclitaxel drugs and immunotherapy has longer mPFS and mOS than that of non-paclitaxel drugs,indicating that the combination of paclitaxel drugs and immunotherapy has better synergy.3.The combination of three immune checkpoint inhibitors(Sintilimab,Camrelizumab,Tislelizumab)and different chemotherapy regimens had no significant effect on the patients’ mPFS and mOS.4.Whether liver metastasis has no significant effect on the efficacy of first-line immunotherapy in patients with advanced gastric cancer.5.In immunotherapy,patients ≤70 years old have longer mPFS than patients>70 years old,and there is no significant difference in mOS between the two,which indicates that age is not a limiting factor affecting the use of immunotherapy.6.The expression of P53 and ERCC1 in gastric cancer tissue is related to the efficacy of chemotherapy combined with immunotherapy. |
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