99P - Impact of single-heterozygous UGT1A1 on the clinical outcomes of nano-liposomal irinotecan plus 5-fluorouracil/leucovorin for patients with pancreatic ductal adenocarcinoma

Background

It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and safety of nanoliposomal irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in advanced pancreatic ductal adenocarcinoma (PDAC).

Methods

We compared the efficacy and safety of nal-IRI+5-FU/LV by UGT1A1 status, WT versus SH, among the patients enrolled in our retrospective cohort study HGCSG2101 which is analyzed real-world data of nal-IRI+5-FU/LV in Japanese patients with PDAC. The median overall survival (OS), progression free survival (PFS) with each 95% confidence interval (CI) were estimated by the Kaplan-Meier method. Tumor response was assessed by RECIST ver. 1.1. Adverse events were evaluated according to CTCAE ver. 5.0.

Results

A total of 48 patients were evaluated (26 and 22 patients with UGT1A1 WT and SH, respectively). The median PFS was 2.8 months (95%CI: 1.85-6.92) in WT group and 2.4 months (95%CI: 1.85-6.00) in SH group, respectively (HR: 1.16, 95%CI: 0.6３–2.14, p=0.63). The median OS was 6.6 months (95%CI: 4.65-11.33) in WT group and 6.8 months (95%CI: 4.26-9.42) in SH group (HR: 1.04, 95% CI: 0.51–2.13, p=0.90), respectively. The response rate was 8.0％ (95%CI: 1.69-26.10) in WT group and 16.7％ (95%CI: 5.01-40.05) in SH group (p= 0.63), respectively. Though there were no significant differences in safety between WT and SH groups, ≥grade3 neutropenia and febrile neutropenia(FN) were observed more frequent in SH group (≥grade3 neutropenia: 30.8% vs 50.0%, p=0.24, FN: 0.0% vs 9.1%, p=0.20, respectively). No treatment-related death was observed in each group.

Conclusions

There was no significant difference in the treatment outcome of nal-IRI+5-FU/LV between UGT1A1 WT and SH groups. However, ≥grade3 neutropenia and FN was more frequent in SH group. Further analysis is needed to investigate the impact of the UGT1A1 status on the treatment outcome of nal-IRI+5-FU/LV for patients with PDAC. These results were previously reported in the ESMO World Congress on Gastrointestinal Cancer 2022 (#SO-30).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hokkaido gastrointestinal cancer study group (HGCSG).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.