Details

Autor(en) / Beteiligte

• Iwasa, Satoru
• Muro, Kei
• Morita, Satoshi
• Park, Young Suk
• Nakamura, Masato
• Kotaka, Masahito
• Nishina, Tomohiro
• Matsuoka, Hiroshi
• Ahn, Joong Bae
• Lee, Keun‐Wook
• Hong, Yong Sang
• Han, Sae Won
• Cho, Sang‐Hee
• Zhang, Dong‐Sheng
• Fang, Wei‐Jia
• Bai, Li
• Yuan, Xiang‐Lin
• Yuan, Ying
• Yamada, Yasuhide
• Sakamoto, Junichi
• Kim, Tae Won

Titel

Impact of UGT1A1 genotype on the efficacy and safety of irinotecan‐based chemotherapy in metastatic colorectal cancer

Ist Teil von

• Cancer science, 2021-11, Vol.112 (11), p.4669-4678

Ort / Verlag

Tokyo: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. Capecitabine plus irinotecan (XELIRI) with or without bevacizumab is noninferior to fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without bevacizumab in terms of overall survival, regardless of UGT1A1 genotype. Additionally, modified XELIRI with or without bevacizumab showed a favorable tolerability profile that was comparable to that of FOLFIRI with or without bevacizumab among all UGT1A1 genotypes.