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
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 re...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-03-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-023-01317-7 |
| _version_ | 1797863402349002752 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Guo-Ming Shi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:36:02Z |
| format | Article |
| id | doaj.art-6f29477f8ecc4e3a86a2432ea36affb9 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-09T22:36:02Z |
| publishDate | 2023-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-6f29477f8ecc4e3a86a2432ea36affb92023-03-22T12:30:38ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352023-03-018111010.1038/s41392-023-01317-7Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 studyGuo-Ming Shi0Xiao-Yong Huang1Dong Wu2Hui-Chuan Sun3Fei Liang4Yuan Ji5Yi Chen6Guo-Huan Yang7Jia-Cheng Lu8Xian-Long Meng9Xin-Ying Wang10Lei Sun11Ning-Ling Ge12Xiao-Wu Huang13Shuang-Jian Qiu14Xin-Rong Yang15Qiang Gao16Yi-Feng He17Yang Xu18Jian Sun19Zheng-Gang Ren20Jia Fan21Jian Zhou22Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Radiology, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Statistics, Zhongshan Hospital, Fudan UniversityDepartment of Pathology, Zhongshan Hospital, Fudan UniversityDepartment of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityTianjin Medical Laboratory, BGI-Tianjin, BGI ShenzhenTianjin Medical Laboratory, BGI-Tianjin, BGI ShenzhenDepartment of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityAbstract 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.https://doi.org/10.1038/s41392-023-01317-7 |
| spellingShingle | 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 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 Signal Transduction and Targeted Therapy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1038/s41392-023-01317-7 |
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