Impact of UGT1A128* polymorphism in patients with metastatic pancreatic ductal adenocarcinoma treated with NALIRIFOX in the NAPOLI 3 trial.

IF 2.6 4区医学 Q2 ONCOLOGY

Future oncology Pub Date : 2026-05-04 DOI:10.1080/14796694.2026.2664776

Maen Abdelrahim, Gazala Khan, Hassan Hatoum, Alice Zervoudakis, Farshid Dayyani, Li Zhang, Jia Li, Fiona Maxwell, Eileen M O'Reilly, Zev A Wainberg, Andrea Bullock

{"title":"Impact of UGT1A1*28 polymorphism in patients with metastatic pancreatic ductal adenocarcinoma treated with NALIRIFOX in the NAPOLI 3 trial.","authors":"Maen Abdelrahim, Gazala Khan, Hassan Hatoum, Alice Zervoudakis, Farshid Dayyani, Li Zhang, Jia Li, Fiona Maxwell, Eileen M O'Reilly, Zev A Wainberg, Andrea Bullock","doi":"10.1080/14796694.2026.2664776","DOIUrl":null,"url":null,"abstract":"Aims: To evaluate the effect of UGT1A1*28 homozygosity on the safety profile of NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in NAPOLI 3 (NCT04083235).Methods: This pre-specified exploratory analysis evaluated safety outcomes by UGT1A1*28 status in patients with mPDAC receiving NALIRIFOX or gemcitabine plus nab-paclitaxel in NAPOLI 3. All patients receiving NALIRIFOX initiated liposomal irinotecan at the full starting dose.Results: Among 749 treated patients, 83 were homozygous for UGT1A1*28. In the NALIRIFOX arm, grade ≥3 and serious treatment-emergent adverse events (TEAEs) related to liposomal irinotecan occurred in 61.5% and 33.3% of patients with homozygous UGT1A1*28 (n = 39), respectively, compared with 63.7% and 22.9% of patients with other genotypes (n = 328). The most common any-grade TEAEs for NALIRIFOX were diarrhea (59.0%), nausea (56.4%), vomiting (46.2%), and anemia (41.0%) in the homozygous group and diarrhea (71.6%), nausea (59.8%), vomiting (38.4%), and decreased appetite (38.1%) in the other genotypes group. Rates of TEAE-related treatment discontinuation and dose reduction/interruption in the NALIRIFOX arm were similar across genotypes.Conclusions: UGT1A1*28 homozygosity was not associated with increased toxicity in patients receiving NALIRIFOX in NAPOLI 3. These findings support the use of full NALIRIFOX dosing irrespective of UGT1A1*28 status.Clinical trial registration: www.clinicaltrials.gov identifier is NCT04083235; EudraCT 2018-003585-14.","PeriodicalId":12672,"journal":{"name":"Future oncology","volume":" ","pages":"1-8"},"PeriodicalIF":2.6000,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14796694.2026.2664776","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aims: To evaluate the effect of UGT1A1*28 homozygosity on the safety profile of NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in NAPOLI 3 (NCT04083235).

Methods: This pre-specified exploratory analysis evaluated safety outcomes by UGT1A1*28 status in patients with mPDAC receiving NALIRIFOX or gemcitabine plus nab-paclitaxel in NAPOLI 3. All patients receiving NALIRIFOX initiated liposomal irinotecan at the full starting dose.

Results: Among 749 treated patients, 83 were homozygous for UGT1A1*28. In the NALIRIFOX arm, grade ≥3 and serious treatment-emergent adverse events (TEAEs) related to liposomal irinotecan occurred in 61.5% and 33.3% of patients with homozygous UGT1A1*28 (n = 39), respectively, compared with 63.7% and 22.9% of patients with other genotypes (n = 328). The most common any-grade TEAEs for NALIRIFOX were diarrhea (59.0%), nausea (56.4%), vomiting (46.2%), and anemia (41.0%) in the homozygous group and diarrhea (71.6%), nausea (59.8%), vomiting (38.4%), and decreased appetite (38.1%) in the other genotypes group. Rates of TEAE-related treatment discontinuation and dose reduction/interruption in the NALIRIFOX arm were similar across genotypes.

Conclusions: UGT1A1*28 homozygosity was not associated with increased toxicity in patients receiving NALIRIFOX in NAPOLI 3. These findings support the use of full NALIRIFOX dosing irrespective of UGT1A1*28 status.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT04083235; EudraCT 2018-003585-14.

查看原文本刊更多论文

在NAPOLI 3试验中，UGT1A1*28多态性对NALIRIFOX治疗的转移性胰腺导管腺癌患者的影响

目的：评价UGT1A1*28纯合性对转移性胰腺导管腺癌（mPDAC）患者NALIRIFOX（伊立替康脂质体+ 5-氟尿嘧啶/亚叶酸蛋白+奥沙利铂）安全性的影响。方法：这项预先指定的探索性分析通过UGT1A1*28状态评估了在NAPOLI 3期接受NALIRIFOX或吉西他滨加nab-紫杉醇治疗的mPDAC患者的安全性结果。所有接受NALIRIFOX治疗的患者起始剂量均为伊立替康脂质体。结果：749例患者中，UGT1A1*28纯合子83例。在NALIRIFOX组中，纯合子UGT1A1*28患者（n = 39）与伊立替康脂质体相关的≥3级和严重治疗发生不良事件（teae）发生率分别为61.5%和33.3%，而其他基因型患者（n = 328）的发生率分别为63.7%和22.9%。NALIRIFOX最常见的teae为纯合子组腹泻（59.0%）、恶心（56.4%）、呕吐（46.2%）和贫血（41.0%），其他基因型组腹泻（71.6%）、恶心（59.8%）、呕吐（38.4%）和食欲下降（38.1%）。在NALIRIFOX组中，teae相关治疗的停药率和剂量减少/中断率在不同基因型中相似。结论：UGT1A1*28纯合性与NAPOLI 3期接受NALIRIFOX的患者毒性增加无关。这些发现支持无论UGT1A1*28状态如何，都应使用NALIRIFOX全剂量。临床试验注册：www.clinicaltrials.gov标识符：NCT04083235；EudraCT 2018-003585-14。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Future oncology ONCOLOGY-

CiteScore

5.40

自引率

3.00%

发文量

335

审稿时长

4-8 weeks

期刊介绍： Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community. The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.