46P - The comparison outcome of GEMOX and PD-1 inhibitors combined with or without lenvatinib for advanced intrahepatic cholangiocarcinoma (ICC): A prospective, single-center, open-label, double-arm phase II trial

Background

Lenvatinib has been identified as a multikinase inhibitor with the effect of inhibiting angiogenesis for advanced ICC. This study aimed to compare the efficacy and safety of GEMOX and PD-1 inhibitors combined with or without lenvatinib as first-line therapy for advanced ICC.

Methods

Eligible participants with treatment naive and diagnosis of unresectable advanced ICC were assigned to G-P-L group: gemcitabine (1000 mg/m²on days 1 and 8 every 3 weeks), oxaliplatin (85 mg/m²on day 1 every 3 weeks), PD-1 inhibitors and lenvatinib (12 mg for weight ≥ 60 kg or 8 mg for weight < 60 kg, once daily), and G-P group: gemcitabine, oxaliplatin and PD-1 inhibitors. The primary endpoints was to assess objective response rate (ORR) evaluated with mRECIST 1.1 and adverse events (AEs). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Genetic mutation biomarkers for lenvatinib were explored using WES.

Results

77 patients were enrolled and divided into G-P-L group (n=38) and G-P group (n=39). The median follow-up time was 23 months. The median PFS were 13 months in the G-P-L group and 7.9 months in the G-P group (hazard ratio[HR]: 0.38, 95% CI: 0.20–0.71, P=0.007). The median OS were 18.5 months in the G-P-L group and 14.6 months in the G-P group (P=0.19). No significant differences of grade ≥ 3 AEs were found between the G-P-L group and the G-P group (68.4% and 64.1%). ORR, DCR were 39.5% and 89.5% in the G-P-L group versus 33.3% and 76.9% in the G-P group, respectively. Multivariate Cox regression analysis indicated that with or without Lenvatinib combination was the independent risk factor of PFS in the entire group (P=0.002). Keap-1 gene mutation was found with significant difference in PR group comparing with SD and PD group in the G-P-L group (P=0.003).

Conclusions

GEMOX combined with PD-1 inhibitor and lenvatinib indicated the feasibility as first-line therapy for advanced ICC with Keap-1 gene mutation. Multi-center with large scale of cases study were needed for further exploration.

Clinical trial identification

NCT05215665.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.