Anti-PD1 antibody toripalimab combined with lenvatinib, or GEMOX chemotherapy combined with lenvatinib as first-line therapy in patients with advanced intrahepatic cholangiocarcinoma: a randomized, open, two-cohort Phase 2 Study.
This research aimed to assess the efficacy and safety of a regimen combining lenvatinib with an anti-PD-1 antibody or chemotherapy in patients with advanced intrahepatic cholangiocarcinoma (ICC).
A two-arm, open-label, phase II trial was carried out. Participants in Arm A received 240 mg of toripalimab intravenously on day 1 of each 3-week cycle, plus daily oral lenvatinib at 8 mg (< 60 kg) or 12 mg (≥60 kg). Participants in Arm B were administered the same daily lenvatinib in combination with GEMOX chemotherapy: 85 mg/m2 oxaliplatin on day 1, and 1 g/m2 gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS).
Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3% (10/31; 95% CI: 16.7%-51.4%), and three patients underwent surgery after tumor downstaging. The median OS was 20.3 months (95% CI: 9.3-27.1), and median PFS was 8.9 months (95% CI: 4.2-13.9). Arm B showed an ORR of 40.0% (12/30; 95% CI: 22.7%-59.4%), and one patient proceeded to surgery after downstaging. Median OS was 15.5 months (95% CI: 9.6-23.8), and median PFS was 8.0 months (95% CI: 5.0-11.4). Adverse events (AEs) related to treatment were observed in most patients, with grade 3-4 AEs in 35.5% of Arm A and 40.0% of Arm B. The most frequent AEs were fatigue (71% vs. 63%), paresthesia (45% vs. 40%), and gingivitis (45% vs. 20%). Grade 4 thrombocytopenia occurred in 6.7% of Arm B. No grade 5 AEs were observed. Peripheral blood analysis showed monocyte levels decreased in PR(partial response) patients in Arm A but increased in PR patients in Arm B.
The Combination of lenvatinib with either anti-PD-1 antibody or GEMOX chemotherapy is a well-tolerated and effective treatment for advanced ICC.
ClinicalTrials.gov, NCT04361331.
A two-arm, open-label, phase II trial was carried out. Participants in Arm A received 240 mg of toripalimab intravenously on day 1 of each 3-week cycle, plus daily oral lenvatinib at 8 mg (< 60 kg) or 12 mg (≥60 kg). Participants in Arm B were administered the same daily lenvatinib in combination with GEMOX chemotherapy: 85 mg/m2 oxaliplatin on day 1, and 1 g/m2 gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS).
Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3% (10/31; 95% CI: 16.7%-51.4%), and three patients underwent surgery after tumor downstaging. The median OS was 20.3 months (95% CI: 9.3-27.1), and median PFS was 8.9 months (95% CI: 4.2-13.9). Arm B showed an ORR of 40.0% (12/30; 95% CI: 22.7%-59.4%), and one patient proceeded to surgery after downstaging. Median OS was 15.5 months (95% CI: 9.6-23.8), and median PFS was 8.0 months (95% CI: 5.0-11.4). Adverse events (AEs) related to treatment were observed in most patients, with grade 3-4 AEs in 35.5% of Arm A and 40.0% of Arm B. The most frequent AEs were fatigue (71% vs. 63%), paresthesia (45% vs. 40%), and gingivitis (45% vs. 20%). Grade 4 thrombocytopenia occurred in 6.7% of Arm B. No grade 5 AEs were observed. Peripheral blood analysis showed monocyte levels decreased in PR(partial response) patients in Arm A but increased in PR patients in Arm B.
The Combination of lenvatinib with either anti-PD-1 antibody or GEMOX chemotherapy is a well-tolerated and effective treatment for advanced ICC.
ClinicalTrials.gov, NCT04361331.
Authors
Huang Huang, Shi Shi, Zheng Zheng, Sun Sun, Liang Liang, Ji Ji, Chen Chen, Yang Yang, Hu Hu, Lu Lu, Meng Meng, Guo Guo, Zhang Zhang, Fan Fan, Zhou Zhou
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