Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-06-04 DOI:10.1093/oncolo/oyaf080

Jean-Frédéric Blanc, Mohamed Bouattour, Ludovic Gauthier, Emmanuel Deshayes, Sophie Guillemard, Yann Touchefeu, Fabienne Portales, Christophe Borg, Lobna Harguem, Rosine Guimbaud, Laurent Mineur, Marc Ychou, Thibault Mazard, Eric Assenat

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Abstract

Background: New therapeutic options are needed for biliary tract cancer (BTC). Regorafenib, a multikinase inhibitor, shows promise in refractory digestive cancers and may be beneficial with conventional chemotherapy for BTC.

Patients and methods: The BREGO study evaluated regorafenib with modified gemcitabine-oxaliplatin (mGEMOX) in advanced or metastatic BTC. Phase I determined the recommended dose (RP2D) of regorafenib (80, 120 or 160 mg, days 1-14) combined with mGEMOX (gemcitabine 900 mg.m-2 IV, 30 min, followed by oxaliplatin 80mg.m-2 IV, 120 min, days 1 and 8). Phase II randomized (1:2) patients to mGEMOX alone (arm A) or mGEMOX + regorafenib (arm B, RP2D, days 1-14), assessing efficacy and safety, with the primary outcome being progression-free survival (PFS). Metabolic tumor features and response were also assessed.

Results: In phase Ib, 22 patients were enrolled; in phase II, 66 patients (arm A, n = 24; arm B, n = 42). Four dose-limiting toxicities were observed, but no maximum tolerated dose was reached. The RP2D was 160 mg.d-1. Median PFS (7.2 vs7.8 months; P = .825) and overall survival (15.1 vs 13.5 months; P = .356) were similar between arms. However, posttreatment 18F-FDG tumor uptake (SULpeak) significantly correlated with PFS (P = .001) and OS (P = .016). Baseline plasma stanniocalcin 1 levels < 265 pg.mL-1 were associated with longer PFS (P = .030) and OS (P = .060) in both arms.

Conclusions: Combining regorafenib and mGEMOX is feasible as first-line treatment for BTC but did not increase PFS as expected in the phase II cohort. Identifying new biomarkers can help target patients with advanced BTCs who may benefit from regorafenib-associated therapy.

Trial registration number: ClinicalTrials.gov, NCT02386397.

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瑞非尼联合改良吉西他滨-奥沙利铂治疗晚期胆道癌患者。随机Ib/II期BREGO研究。

背景：胆道癌（BTC）需要新的治疗方案。Regorafenib是一种多激酶抑制剂，在难治性消化系统癌症中显示出希望，并且可能对BTC的常规化疗有益。患者和方法：BREGO研究评估了瑞非尼与改良吉西他滨-奥沙利铂（mGEMOX）治疗晚期或转移性BTC的疗效。I期试验确定regorafenib（80,120或160 mg，第1-14天）联合mGEMOX（吉西他滨900 mg）的推荐剂量（RP2D）。m- 2iv, 30min，随后给予奥沙利铂80mg。m-2静脉注射，120分钟，第1、8天)。II期随机（1:2）患者接受mGEMOX单独治疗（A组）或mGEMOX + regorafenib （B组，RP2D，第1-14天），评估疗效和安全性，主要终点为无进展生存期（PFS）。还评估了代谢性肿瘤的特征和反应。结果：在Ib期，22例患者入组；在II期，66例患者(A组，n = 24；B组，n = 42)。观察到四种剂量限制性毒性，但没有达到最大耐受剂量。RP2D为160 mg.d-1。中位PFS (7.2 vs7.8个月；P = .825)和总生存期(15.1 vs 13.5个月；P = .356)组间相似。然而，治疗后18F-FDG肿瘤摄取（SULpeak）与PFS （P = .001）和OS （P = .016）显著相关。结论：瑞非尼联合mGEMOX作为BTC的一线治疗是可行的，但在II期队列中并没有像预期的那样增加PFS。确定新的生物标志物可以帮助晚期btc患者从瑞非尼相关治疗中获益。试验注册号：ClinicalTrials.gov, NCT02386397。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.