TY - JOUR
T1 - Impact of UGT1A1 genotype on the efficacy and safety of irinotecan-based chemotherapy in metastatic colorectal cancer
AU - Iwasa, Satoru
AU - Muro, Kei
AU - Morita, Satoshi
AU - Park, Young Suk
AU - Nakamura, Masato
AU - Kotaka, Masahito
AU - Nishina, Tomohiro
AU - Matsuoka, Hiroshi
AU - Ahn, Joong Bae
AU - Lee, Keun Wook
AU - Hong, Yong Sang
AU - Han, Sae Won
AU - Cho, Sang Hee
AU - Zhang, Dong Sheng
AU - Fang, Wei Jia
AU - Bai, Li
AU - Yuan, Xiang Lin
AU - Yuan, Ying
AU - Yamada, Yasuhide
AU - Sakamoto, Junichi
AU - Kim, Tae Won
N1 - Funding Information:
We thank the Scientific Publications Team and Joon Seo Lim at Asan Medical Center for their editorial assistance. This trial was sponsored by the Epidemiological and Clinical Research Information Network (ECRIN: global sponsor), the Asan Medical Center Academic Research Office, and the Sun Yat‐sen University Cancer Center, and was funded by Chugai Pharmaceutical and F Hoffmann‐La Roche.
Funding Information:
Satoru Iwasa reported receiving honoraria from Chugai and Taiho and research funding from Daiichi Sankyo and Pfizer. Kei Muro reported receiving honoraria from Chugai and Taiho and research funding from Daiichi Sankyo, Pfizer, and Taiho. Satoshi Morita reported receiving honoraria from Chugai, Pfizer, and Taiho. Masato Nakamura reported receiving honoraria from Chugai, Yakult Honsha, and Taiho. Masahito Kotaka reported receiving honoraria from Chugai and Yakult Honsha. Tomohiro Nishina reported receiving honoraria from Chugai and Taiho and research funding from Chugai, Daiichi Sankyo, and Taiho. Keun‐Wook Lee reported receiving honoraria from Genexine, MedPacto, and ISU abxis. Yasuhide Yamada reported receiving honoraria from Chugai, Nipponkayaku, and Taiho and grants from Daiichi Sankyo. Junichi Sakamoto reported receiving an honorarium from Chugai. The other authors have no conflicts of interest to declare.
Funding Information:
Epidemiological and Clinical Research Information Network; Asan Medical Center Academic Research Office; Sun Yat-sen University Cancer Center; Chugai Pharmaceutical; F Hoffmann-La Roche. We thank the Scientific Publications Team and Joon Seo Lim at Asan Medical Center for their editorial assistance. This trial was sponsored by the Epidemiological and Clinical Research Information Network (ECRIN: global sponsor), the Asan Medical Center Academic Research Office, and the Sun Yat-sen University Cancer Center, and was funded by Chugai Pharmaceutical and F Hoffmann-La Roche.
Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2021/11
Y1 - 2021/11
N2 - The phase III AXEPT study showed the noninferiority of modified capecitabine plus irinotecan (mXELIRI) with or without bevacizumab relative to fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without bevacizumab as a second-line treatment for metastatic colorectal cancer. We evaluated the associations between the UGT1A1 genotype linked to adverse events—caused by irinotecan—and the efficacy and safety of mXELIRI and FOLFIRI. The UGT1A1 genotype was prospectively determined and patients were categorized into three groups according to WT (*1/*1), single heterozygous (SH; *28/*1 or *6/*1), and double heterozygous or homozygous (DHH; *28/*28, *6/*6, or *28/*6). Overall survival (OS), progression-free survival, response rate, and safety were assessed. The UGT1A1 genotype was available in all 650 randomized patients (WT, 309 [47.5%]; SH, 291 [44.8%]; DHH, 50 [7.7%]). The median OS was 15.9, 17.7, and 10.6 months in the WT, SH, and DHH groups, respectively, with an adjusted hazard ratio (HR) of 1.53 (95% confidence interval [CI], 1.12-2.09; P =.008) for DHH vs WT or SH. The median OS in the mXELIRI and FOLFIRI arms was 18.1 vs 14.3 months (HR 0.80; 95% CI, 0.62-1.03) in the WT group, 16.3 vs 18.3 months (HR 1.04; 95% CI, 0.79-1.36) in the SH group, and 13.0 vs 9.1 months (HR 0.71; 95% CI, 0.39-1.31) in the DHH group, respectively. Modified capecitabine plus irinotecan with or without bevacizumab could be a standard second-line chemotherapy in terms of efficacy and safety regardless of the UGT1A1 genotype.
AB - The phase III AXEPT study showed the noninferiority of modified capecitabine plus irinotecan (mXELIRI) with or without bevacizumab relative to fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without bevacizumab as a second-line treatment for metastatic colorectal cancer. We evaluated the associations between the UGT1A1 genotype linked to adverse events—caused by irinotecan—and the efficacy and safety of mXELIRI and FOLFIRI. The UGT1A1 genotype was prospectively determined and patients were categorized into three groups according to WT (*1/*1), single heterozygous (SH; *28/*1 or *6/*1), and double heterozygous or homozygous (DHH; *28/*28, *6/*6, or *28/*6). Overall survival (OS), progression-free survival, response rate, and safety were assessed. The UGT1A1 genotype was available in all 650 randomized patients (WT, 309 [47.5%]; SH, 291 [44.8%]; DHH, 50 [7.7%]). The median OS was 15.9, 17.7, and 10.6 months in the WT, SH, and DHH groups, respectively, with an adjusted hazard ratio (HR) of 1.53 (95% confidence interval [CI], 1.12-2.09; P =.008) for DHH vs WT or SH. The median OS in the mXELIRI and FOLFIRI arms was 18.1 vs 14.3 months (HR 0.80; 95% CI, 0.62-1.03) in the WT group, 16.3 vs 18.3 months (HR 1.04; 95% CI, 0.79-1.36) in the SH group, and 13.0 vs 9.1 months (HR 0.71; 95% CI, 0.39-1.31) in the DHH group, respectively. Modified capecitabine plus irinotecan with or without bevacizumab could be a standard second-line chemotherapy in terms of efficacy and safety regardless of the UGT1A1 genotype.
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U2 - 10.1111/cas.15092
DO - 10.1111/cas.15092
M3 - Article
C2 - 34327766
AN - SCOPUS:85113946002
VL - 112
SP - 4669
EP - 4678
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 11
ER -