Clinical Efficacy And Safety Analysis Of Intratumoral Injection Of PD-(L)1 Inhibitors Combined With Chemotherapy For Advanced Solid Tumors

Objective:The study was aimed to explore the clinical efficacy and safety of intratumoral injection of PD-(L)1 inhibitors combined with chemotherapy for advanced solid tumors through fine needle puncture.Data and Methods:A phase Ⅱ clinical trail was registered on Clinical Trail.gov(ID:NCT03755739),on 2018 and data of 44 patients with advanced solid tumors who received PD-(L)1 inhibitors combined with chemotherapy from April 2020 to October2022 were collected.Clinical data,safety and efficacy of patients were collected and analyzed.According to the immunotherapy Response Evaluation Criteria in Solid Tumor,the efficacy data was based on the best response,including complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD).The main responses included objective response rate(ORR),disease control rate(DCR),overall response(OS)and profession-free survival(PFS).Fisher’s exact probability method was used to compare differences between groups.The Kaplan-Meier method was used to estimate the median overall survival(m OS)and median profession-free survival(m PFS).The potential prognostic factors for PFS were determined by multivariate Cox proportional risk regression model.Adverse events were classified and graded according to Common Terminology Classification Adverse Events version5.0(CTCAE V5.0).Results:A total of 44 patients with advanced solid tumors who received 156 treatment cycles from April 2020 to October 2022,were enrolled in this study.The most frequencies of primary tumors were lung cancer(n=13),liver cancer(n=10),colorectum cancer(n=10).The most commonly injected tumor sites were liver(30.5%),lung(16.0%),bone(15.5%),deep lymph nodes(14.5%).Injected tumors’ median diameter was 43.4mm(IQR: 29.6-76.5),and a median number of treatments per patients was 3(IQR: 2-4).The median OS and median PFS were 8.3 months(95%CI: 5.0-11.6)and 6.3 months(95%CI: 3.6-9.0),respectively.According to i RECIST criteria,the best systemic response was 1 complete response,13 partial response,24 stable disease and 6 patients had a progression disease as best response.The ORR and DCR were 31.8% and 86.3%,respectively.Cox regression analyses showed that previous systemic immunotherapy,injected tumors with diameter greater than 50 mm,metastatic tumors with burden greater than 2 were the independent risk factors for PFS.Procedure-related adverse events(AEs)occurred in 18% of the treatment cycles,among which pain was the most common adverse event.All patients occurred treatment-related adverse events.In all 156 cycles,the most common treatment-related adverse events of grade 1-2 and 3-4 were fever(41.6%)and thrombocytopenia(6.4%),respectively.One patient was died for severe immune-related dermatitis.Conclusion:Intratumoral administration of PD-(L)1 inhibitors combined with chemotherapy has good efficacy,feasibility and controllable safety for advanced tumors,and further randomized clinical trials are still needed to evaluate this treatment regime.