Blanc Jean-Frédéric, Bouattour Mohamed, Gauthier Ludovic, Deshayes Emmanuel, Guillemard Sophie, Touchefeu Yann, Portales Fabienne, Borg Christophe, Harguem Lobna, Guimbaud Rosine, Mineur Laurent, Ychou Marc, Mazard Thibault, Assenat Eric
Department of Hepato-Gastroenterology and Medical Oncology, University of Bordeaux Hospital, Haut Leveque Hospital, 33600 Pessac, France.
AP-HP, Liver Cancer and Innovative Therapy, Beaujon Hospital, 92110 Clichy, France.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf080.
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.
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.
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.
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.
ClinicalTrials.gov, NCT02386397.
胆道癌（BTC）需要新的治疗选择。瑞戈非尼是一种多激酶抑制剂，在难治性消化系统癌症中显示出前景，对于BTC联合传统化疗可能有益。
BREGO研究评估了瑞戈非尼联合改良吉西他滨-奥沙利铂（mGEMOX）用于晚期或转移性BTC。I期确定了瑞戈非尼（80、120或160mg，第1 - 14天）联合mGEMOX（吉西他滨900mg.m-2静脉滴注，30分钟，随后奥沙利铂80mg.m-2静脉滴注，120分钟，第1天和第8天）的推荐剂量（RP2D）。II期将患者随机（1:2）分为单独使用mGEMOX（A组）或mGEMOX + 瑞戈非尼（B组，RP2D，第1 - 14天），评估疗效和安全性，主要结局为无进展生存期（PFS）。还评估了代谢肿瘤特征和反应。
在Ib期，入组22例患者；在II期，66例患者（A组，n = 24；B组，n = 42）。观察到4例剂量限制性毒性，但未达到最大耐受剂量。RP2D为160mg.d-1。两组之间的中位PFS（7.2对7.8个月；P = 0.825）和总生存期（15.1对13.5个月；P = 0.356）相似。然而，治疗后18F - FDG肿瘤摄取（SULpeak）与PFS（P = 0.001）和OS（P = 0.016）显著相关。在两组中，基线血浆骨钙素1水平<265pg.mL-1与更长的PFS（P = 0.030）和OS（P = 0.060）相关。
联合瑞戈非尼和mGEMOX作为BTC的一线治疗是可行的，但在II期队列中未如预期增加PFS。识别新的生物标志物有助于确定可能从瑞戈非尼相关治疗中获益的晚期BTC患者。
ClinicalTrials.gov，NCT02386397。
Zotero 插件
