The Efficacy And Safety Of PD-1 Inhibitors Alone Or In Combination With Radiotherapy In Malignant Melanoma: A Secondary Analysis

Objective: Compared with programmed death receptor-1(PD-1)inhibitors,PD-1 inhibitors combined with radiotherapy have synergistic effect on malignant melanoma.However,the specific efficacy and safety are not clear.We made a secondary analysis to compare the efficacy and safety of PD-1 inhibitors alone with combined radiotherapy.Methods: PubMed databases were searched January 2010 to December 2018.Eligible studies included randomized controlled trials(RCTs)in regard to PD-1 inhibitors alone and combination with radiotherapy in malignant melanoma patients reporting the evaluation of short-term,long-term effects and any all-grades(1–4)treatment-related adverse events(AEs),immune-related adverse events(irAEs)and treatment related deaths.Calculate and compare the incidence rate of them.To evaluate whether combination of PD-1 inhibitors and radiotherapy can improve the efficacy and increase the risk of treatment-related AEs and irAEs.Results: A total of 2776 patients from 10 RCTs were included in the secondary analysis: PD-1 Inhibitors alone(7 trials)and PD-1 Inhibitors in combination with radiotherapy(3 trials).Compared with the single drug PD-1 inhibitor,the complete response(CR)rate of PD-1 inhibitor combined with radiotherapy was significantly improved(P<0.05);There was no significant difference in the risk of pruritus,diarrhea,arthralgia,vomiting,vitiligo,elevated liver enzymes and hypothyroidism in all grades(1-4)and high grades(3-4)of combination of PD-1 inhibitor and radiotherapy compared with single drug use of PD-1 inhibitor;The combination of PD-1 inhibitors and radiotherapy increases the risk of alopecia in low grades(1-2),nausea and rash in high grades(3-4)(P<0.05).Conclusions: In general,the combination of PD-1 inhibitor and radiotherapy can improve efficacy and the risk of individual adverse reactions related to the treatment has increased,but no significant serious adverse reactions have been found,the incidence of high-levels(3-4)adverse events was low,within the tolerable range.