Meta-analysis Of The Efficacy And Safety Of PD-1 Inhibitors In The Treatment Of Advanced Tumors

Objective:To systematic evaluate the efficacy and safety of PD-1 inhibitors in the treatment of advanced non-small cell lung cancer(ANSCLE)and advanced melanoma(AM).Method:Randomized controlled trials were included after searching keywords in various Chinese and English databases and selecting documents.The quality of the included literature was evaluated according to the Cochrane bias risk assessment criteria,and Rev Man5.3 was used to perform a Meta-analysis of the overall survival,progressionfree survival,incidence of adverse reactions,and incidence of grade 3-5 adverse reactions in the included studies.Result:A total of 7 randomized controlled trials(RCT)were included in this study.Four RCTs of them are for the treatment of ANSCLC,while three RCTs for AM.Compared with docetaxel,PD-1 inhibitors can effectively improve the overall survival of patients [HR = 0.67,95% CI(0.61,0.74),P <0.00001] and progression-free survival [HR = 0.80,95% CI(0.73,0.88),P <0.00001].The results of the safety of PD-1 inhibitors in the treatment of ANSCLC were list as follows.(1)As to digestive system adverse drug reaction(ADR),the incidences of nausea and appetite decline in the PD-1 inhibitor group are significantly lower than that in the docetaxel group,in which the incidences of nausea and appetite decline in grade 3-5 are similar to the docetaxel group,while the incidence of diarrhea and grade 3-5 diarrhea in the PD-1 inhibitor group are significantly lower than those in the docetaxel group.(2)As to hematological system ADR,the incidences of anemia,leukopenia,neutropenia and febrile neutropenia in the PD-1 inhibitor group are significantly lower than those in the docetaxel group,while the incidences of anemia,leukopenia,neutropenia and febrile neutropenia in grade 3-5 are significantly lower than those in the docetaxel group.(3)As to respiratory system ADR,the incidence of pneumonitis in the PD-1 inhibitor group is higher than that in the docetaxel group,in which the incidence of pneumonitis in grades 3-5 is similar to the docetaxel group.(4)As to skin system ADR,the incidence of rash and grade 3-5 rash in the PD-1 inhibitor group are similar to the docetaxel group,while the incidence of alopecia in the PD-1 inhibitor group is significantly lower than that in the docetaxel group,in which the incidence of alopecia in grades 3-5 is similar to the docetaxel group.(5)As to motor system ADR,the incidence of fatigue and grade 3-5 fatigue in the PD-1 inhibitor group are significantly lower than those in the docetaxel group,while the incidence of asthenia and grade 3-5 asthenia in the PD-1 inhibitor group are significantly lower than those in the docetaxel group,and the incidence of myalgia in the PD-1 inhibitor group is significantly lower than that in the docetaxel group,in which the incidence of myalgia in grades 3-5 is similar to the docetaxel group.Compared with ipilimumab,PD-1 inhibitors can effectively improve the overall survival of patients[HR = 0.66,95% CI(0.57,0.75),P <0.00001] and progression-free survival [HR = 0.57,95% CI(0.50,0.64),P <0.00001].The results of the safety of PD-1 inhibitors in the treatment of AM were list as follows.(1)As to digestive system ADR,the incidence of nausea and grade 3-5 nausea in the PD-1 inhibitor group are similar to the ipilimumab group,while the incidence of diarrhea and grade 3-5 diarrhea in the PD-1 inhibitor group are lower than those in the ipilimumab group,and the incidence of abdominal pain in the PD-1 inhibitor group is lower than that in the ipilimumab group,in which the incidence of abdominal pain in grade 3-5 is similar to the ipilimumab group,and the incidence of colitis and grade 3-5 colitis in the PD-1 inhibitor group are lower than those in the ipilimumab group,and the incidences of increase in ALT,AST levels and grade 3-5 increases in ALT,AST levels in the PD-1 inhibitor group are similar to the ipilimumab group.(2)As to endocrine system ADR,the incidences of hypothyroidism and hyperthyroidism in the PD-1 inhibitor group are higher than that in the ipilimumab group,in which the incidences of hypothyroidism and hyperthyroidism in grade 3-5 are similar to the ipilimumab group,while the incidence of hypophysitis is similar to the ipilimumab group,in which the incidence of hypophysitis in grade 3-5 is lower than that in the ipilimumab group.(3)As to respiratory system ADR,the incidence of pneumonitis and grade 3-5 pneumonitis in the PD-1 inhibitor group are similar to the ipilimumab group.(4)As to skin system ADR,the incidence of rash is similar to the ipilimumab group,in which the incidence of rash in grade 3-5 is lower than that in the ipilimumab group,while the incidences of maculopapular rash and pruritus in the PD-1 inhibitor group are lower than that in the ipilimumab group,in which the incidences of maculopapular rash and pruritus in grade 3-5 are similar to the ipilimumab group,and the incidence of vitiligo in the PD-1 inhibitor group is higher than that in the ipilimumab group,in which the incidence of vitiligo in grade 3-5 is similar to the ipilimumab group.(5)As to motor system ADR,the incidences of fatigue and asthenia in the PD-1 inhibitor group are higher than that in the ipilimumab group,in which the incidences of fatigue and asthenia in grade 3-5 are similar to the ipilimumab group,while the incidence of arthralgia in the PD-1 inhibitor group is higher than that in the ipilimumab group,in which the incidence of arthralgia in grade 3-5 is similar to the ipilimumab group.(6)Other ADR: the incidence of headache and grade 3-5 headache in the PD-1 inhibitor group are similar to the ipilimumab group,while the incidence of maculopapular and grade 3-5 maculopapular in the PD-1 inhibitor group are similar to the ipilimumab group.Conclusion:In terms of effacy,taking the incidence of adverse drug reactions as a measure,the effectiveness of PD-1 inhibitors in the treatment of ANSCLC and AM are better than that in the control group.In terms of safety,taking the overall ADR and the grade 3-5 overall ADR as a measure,compared with the docetaxel group,the incidence of overall ADR and grade 3-5 overall ADR in the PD-1 inhibitor group were significantly reduced.Compared with the ipilimumab group,the incidence of overall ADR in the PD-1 inhibitor group is similar,while the incidence of grade 3-5 overall ADR in the PD-1 inhibitor group is significantly reduced.