52P - HGCSG1901: A retrospective cohort study evaluating the safety and efficacy of S-1 and irinotecan plus bevacizumab in patients with metastatic colorectal cancer - Impact of single-heterozygous UGT1A1 on the clinical outcomes

Background

Irinotecan and S-1 plus bevacizumab (IRIS/Bev) is one of the standards first line (1L) or second line (2L) treatments for patients with metastatic colorectal cancer (mCRC). We have previously reported the real-world clinical data of IRIS/Bev in Japanese patients with mCRC (HGCSG1901). Herein we compared the efficacy and safety of IRIS/Bev in 1L or 2L treatment by UGT1A1 status, wild type (WT) versus single heterozygous (SH), among the patients enrolled in the HGCSG1901.

Methods

We retrospectively collected the clinical data of 415 patients who received IRIS/Bev for mCRC at 24 institutions from August 2011 to March 2019. In this analysis, we extracted only UGT1A1 WT and SH patients and compared them. The median overall survival (OS) and progression free survival (PFS) were estimated by the Kaplan-Meier method, and compared between WT and SH by Log-rank test and Cox regression analysis. Tumor response was assessed by RECIST ver. 1.1. Adverse events were evaluated according to CTCAE ver. 5.0.

Results

A total of 213 patients were evaluated (130 and 83 patients with UGT1A1 WT and SH, respectively). The median relative dose intensity of irinotecan was 0.77 (range, 0.36-1.12) in WT and 0.78 (range, 0.06-1.06) in SH, respectively (p=0.358). The median PFS in 1L/2L were 14.8/7.1 months in WT and 18.2/7.6 months in SH, respectively (1L: HR 0.696, p=0.295, 2L: HR 0.763, p=0.125). The median OS in 1L/2L were 32.9/15.8 months in WT and 47.8/18.3 months in SH (1L: HR 0.675, p=0.315, 2L: HR 0.830, p=0.298), respectively. There was significant differences in ≥grade3 neutropenia between WT and SH (WT 13.2 vs SH 34.9%, p=0.001). There was no significant difference between the two groups regarding diarrhea.

Conclusions

There were no significant differences in the efficacy outcomes of IRIS/Bev between WT and SH. However, ≥grade 3 neutropenia was observed significantly more frequent in SH. It is necessary to pay attention to neutropenia when administering IRIS/Bev to patients with SH.

Clinical trial identification

UMIN000039077 2020/1/8.

Editorial acknowledgement

Legal entity responsible for the study

Nonprofit organization, Hokkaido Gastrointestinal Cancer Study Group.

Funding

Nonprofit organization, Hokkaido Gastrointestinal Cancer Study Group.

Disclosure

S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eli Lilly K.K., Takeda Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Bristol Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Merck Biopharma Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd. Y. Kawamoto: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Yakult Honsha Co., Ltd., Merck KGaA, Incyte Biosciences Japan, Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Funding: Takeda Pharmaceutical Co., Ltd. K. Sawada: Financial Interests, Personal, Invited Speaker: Ono, Chugai, Daiichi-Sankyo, Lilly, Asahi-Kasei, Merck, Takeda, Taiho. M. Nakamura: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly Japan K.K., Takeda, Taiho, Sanofi, Bristol Myers Squibb, Bayer Yakuhin, Ono, Yakult Honsha. H. Nakatsumi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bayer Yakuhin, Lilly Japan, Sanofi, Taiho Pharmaceutical. All other authors have declared no conflicts of interest.