Application Of Immune Checkpoint Inhibitors In The Treatment Of Advanced Pancreatic Cancer

Objectives To investigate the efficacy and safety of three immune checkpoint inhibitors,Sintilimab,Toripalimab and Camrelizumab,in the treatment of advanced pancreatic cancer patients who failed first-line chemotherapy.Methods Patients with advanced pancreatic cancer who failed first-line therapy from Tangshan Workers’ Hospital,Kailuan General Hospital and Tangshan Nanhu Hospital from January 2019 to December 2021 were collected,and the clinical treatment regimen included intravenous infusion of one of the three PD-1 mabs as the observation subjects.Objective response rate,disease control rate,progression free survival,overall survival,change of CA19-9 values,physical state change,and adverse events were followed up,and compared with patients receiving second-line chemotherapy alone.Results A total of 27 patients with advanced pancreatic cancer treatmented with immunotherapy(observation group)and 16 patients with advanced pancreatic cancer treatmented with chemotherapy alone(control group)were collected.Up to February 2022,23 and 14 patients in the two groups reached the end point of death,respectively.Objective response rate and disease control rate were 25.9% and 18.8%,63% and 31.3%,respectively.The median progression free survival was 4.8 months(95%CI:3.303-5.300)and 4.05 months(95%CI:2.900-5.100);the median overall survival was 6.6 months(95%CI:3.200-6.800)and 5.7 months(95%CI:4.451-6.600).Hematotoxicity,including leukopenia,granulocytopenia,thrombocytopenia and anemia,remains the most common adverse reactions.All immune-related adverse events occurred in the observation group,including 6 cases(22.2%)of grade 1～2 transient fever,4 cases(14.8%)of rash,1 case(3.7%)of grade 3,3 cases(11.1%)of grade 1～2 capillary hyperplasia,and 1 case(3.7%)of asymptomatic hypothyroidism(grade 1).1 suspected immune-related pneumonia(grade1);other major adverse events that occurred in excess of 10% included nausea and vomiting,diarrhea,constipation,fatigue,and elevated transaminases and bilirubin.Progression free survival univariate survival analysis suggested that patients with ECOG score of 0～1(5.1 months vs 2.2 months,P=0.000),patients with number of metastasis of 0～2(5.1 months vs 2.95 months,P=0.010),patients with combined radiotherapy(5.1 months vs 4.75 months,P=0.016),patients without liver metastasis(5.1months vs 3.25 months,P=0.005)had significantly longer progression free survival.Baseline characteristics such as gender(P=0.555),age(P=0.359),combined chemotherapy(P=0.200),CA19-9 value(P=0.752),surgery(P=0.491),and treatment line number(P=0.154)were not correlated with progression free survival.Conclusions Immune checkpoint inhibitors can be used as a treatment option for advanced pancreatic cancer patients with first-line treatment failure.Their disease control rate is significantly higher than that of patients with second-line chemotherapy alone at the same time,and their safety is predictable,which can improve the quality of life of patients.Due to the small sample size,the clinical value needs to be confirmed by further prospective studies with large samples.Figure 16;Table 6;Reference 97...