摘要
Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ICC.Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine(1 g/m2)on Days 1 and 8 and oxaliplatin(85 mg/m2)Q3W for six cycles along with intravenous toripalimab(240 mg)Q3W and oral lenvatinib(8 mg)once daily for one year.The expression of programmed death-ligand 1(PD-L1)and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing(WES)analysis.The primary endpoint was the objective response rate(ORR).Secondary outcomes included safety,overall survival(OS),progression-free survival(PFS),disease control rate(DCR)and duration of response(DoR).As of July 1,2022,the median follow-up time was 23.5 months,and the ORR was 80%.Twenty-three patients achieved partial response,and one achieved complete response.Patients(21/30)with DNA damage response(DDR)-related gene mutations showed a higher ORR,while patients(14/30)with tumor area positivity≥1(PD-L1 staining)showed a trend of high ORR,but without significant difference.The median OS,PFS,and DoR were 22.5,10.2,and 11.0 months,respectively.The DCR was 93.3%.Further,56.7%of patients experienced manageable grade≥3 adverse events(AEs),commonly neutropenia(40.0%)and leukocytopenia(23.3%).In conclusion,toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC.A phase-III,multicenter,double-blinded,randomized study to validate our findings was approved by the National Medical Products Administration(NMPA,No.2021LP01825).
基金
National Natural Science Foundation of China(81972232,81830102,82150004)
Clinical Research Plan of SHDC(SHDC‑2020CR1003A,SHDC-2020CR1022B)
National Key Research and Development Program of China(2019YFC1316000,2019YFC1315800,and 2019YFC1315802)
the Key Disease Joint Research Program of Xuhui District(XHLHGG202103),the Clinical Medicine Research Pilot Project of Shanghai Medical School of Fudan University(2020,21DGF501035/00)
the Shanghai Municipal Natural Science Foundation(20JC1419103,21ZR1412200)
Beijing Mutual Care Public Welfare Foundation(GDXZ-08-05)Sanming Project of Medicine in Shenzhen(SZSM202003009),and Shanghai Municipal Key Clinical Specialty Construction Project(shslczdzk02401).
