740P - The impact of UGT1A1 genetic polymorphism on safety in unresectable pancreatic cancer patients receiving FOLFIRINOX therapy: A subset analysis of JASPAC 06 study

Abstract

Background: UGT1A1*6 and UGT1A1*28 polymorphisms were reported to be associated with increased irinotecan-induced neutropenia. The aim of this subset analysis is to investigate the association between these polymorphisms and toxicities in patients (pts) treated with FOLFIRINOX in the JASPAC 06 study. Methods: JASPAC 06 study was a nationwide multicenter observational study of FOLFIRINOX for unresectable and recurrent pancreatic cancer. Pts who were screened for UGT1A1*6 and UGT1A1*28, and treated with either original FOLFIRINOX regimen (Oxaliplatin 85 mg/m2, Irinotecan 180 mg/m2, Levofolinate calcium [l-LV] 200 mg/m2, bolus 5-FU 400 mg/m2, and continuous 5-FU 2,400 mg/m2, every two weeks) or modified regimen (Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2, l-LV 200 mg/m2, and continuous 5-FU 2,400 mg/m2, every two weeks) as first-line chemotherapy, were analyzed in this analysis. Results: Of 399 eligible pts enrolled in JASPAC 06 study, 203 pts were eligible in this analysis. UGT1A1 was reported as wild (W) type (-/-) in 118 pts and heterozygous (H) type (-/*6, -/*28) in 81 pts. Remaining four pts with homozygote (*6/*6, *28/*28) or compound heterozygote (*6/*28) were excluded because of small population. Among 199 pts, 79 pts were treated with original regimen and 120 pts with modified regimen. In the original FOLFIRINOX group, 54/25 pts were W/H type. The median age was 60.5/60 years and PS0 was 57/52%. Incidences of grade 3/4 leukopenia, neutropenia, febrile neutropenia, diarrhea, anorexia and grade 4 neutropenia in pts with W/H type were 28/44%, 59/68%, 24/40%, 4/20%, 9/24% and 24/40%, respectively. In the modified FOLFIRINOX group, 64/56 pts were W/H type. The median age was 62.5/62 years and PS0 was 70/70%. The same toxicities as above were 22/27%, 44/50%, 5/7%, 16/7%, 14/9% and 16/20%, respectively. Conclusions: Treated with original FOLFIRINOX regimen, pts with UGT1A1 heterozygous type experienced severe toxicities more frequently than those with wild type. In such cases, careful management of not only hematologic but gastrointestinal toxicities seems to be needed. Legal entity responsible for the study: Shizuoka Industrial Foundation Pharma Valley Center Funding: Diichi Sankyo Co. Ltd Yakult Honsha Co. Ltd Disclosure: H. Fujii: Research funding: Yakult Honsha, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Eizai, Merck, and Kyowa-Hakko Kirin, Co., Ltd. N. Mizuno: Research funding: Zeria Pharmaceutical, Taiho Pharmaceutical Co. Ltd., Merck Serono, AstraZeneca, NanoCarrier, Eisai, and MSD. Honoraria: Yakult Honsha Co., Ltd, Taiho Pharmaceutical Co. Ltd., Novartis, Pfizer, and Kyowa-Hakko Kirin. H. Ueno: Honoraria: Yakult Honsha Co., Ltd Research Funding: Yakult Honsha Co., Ltd. S. Kobayashi: Yakult Honsha (Honoraria). N. Okano: Research Funding: Yakult Honsha Co., Ltd, Daiichi Sankyo Co., Ltd. H. Takafumi: Employee of Daiichi Sankyo Co., Ltd. T. Henmi: Employee of Yakult Honsha Co.,Ltd. A. Todaka: Honoraria:Yakult Honsha Co.,Ltd, Daiichi Sankyo Co., Ltd. A. Fukutomi: Honoraria: Yakult Honsha Co.,Ltd, Daiichi Sankyo Co., Ltd. Advisory Role from Yakult Honsha Co.,Ltd. All other authors have declared no conflicts of interest.