Signal Transduction and Targeted Therapy (Mar 2023)

Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study

  • Guo-Ming Shi,
  • Xiao-Yong Huang,
  • Dong Wu,
  • Hui-Chuan Sun,
  • Fei Liang,
  • Yuan Ji,
  • Yi Chen,
  • Guo-Huan Yang,
  • Jia-Cheng Lu,
  • Xian-Long Meng,
  • Xin-Ying Wang,
  • Lei Sun,
  • Ning-Ling Ge,
  • Xiao-Wu Huang,
  • Shuang-Jian Qiu,
  • Xin-Rong Yang,
  • Qiang Gao,
  • Yi-Feng He,
  • Yang Xu,
  • Jian Sun,
  • Zheng-Gang Ren,
  • Jia Fan,
  • Jian Zhou

DOI
https://doi.org/10.1038/s41392-023-01317-7
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 10

Abstract

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Abstract 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). Trial registration Clinical trials: NCT03951597.