Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
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DOI：
10.1200/jco.21.00679
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发表时间：
2022-01-20
影响因子：
45.3
通讯作者：
Malka, David
中科院分区：
文献类型：
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作者：
Phelip, Jean marc;Desrame, Jerome;Malka, David
目的 对于晚期胆道癌 (BTC)，三联化疗是否优于双联化疗尚不清楚。方法 在这项开放标签、随机 II-III 期研究中，局部晚期或转移性 BTC 且东部肿瘤合作组体能状态为 0 或 1 的患者被随机分配 (1:1) 接受奥沙利铂、伊立替康和输注氟尿嘧啶 (mFOLFIRINOX) 或顺铂和吉西他滨 (CISGEM) 治疗，最长 6 个月。我们报告了 II 期部分的结果，其中主要终点是根据实体瘤 1.1 版疗效评估标准接受至少一剂治疗的患者（改良意向治疗人群）的 6 个月无进展生存率 (PFS)（统计假设：6 个月 PFS 率 >= 59%，预期 73%）。结果 共有 191 名患者（改良意向治疗人群，185 名：mFOLFIRINOX，92 名；CISGEM，93 名）被随机分配到 43 个法国中心。中位随访 21 个月后，mFOLFIRINOX 组的 6 个月 PFS 率为 44.6%（90% CI，35.7 至 53.7），CISGEM 组为 47.3%（90% CI，38.4 至 56.3）。 mFOLFIRINOX 组的中位 PFS 为 6.2 个月（95% CI，5.5 至 7.8），CISGEM 组为 7.4 个月（95% CI，5.6 至 8.7）。 mFOLFIRINOX 组的中位总生存期为 11.7 个月（95% CI，9.5 至 14.2），CISGEM 组的中位总生存期为 13.8 个月（95% CI，10.9 至 16.1）。 mFOLFIRINOX 组中 72.8% 的患者和 CISGEM 组中 72.0% 的患者发生≥ 3 级的不良事件（毒性死亡：mFOLFIRINOX 组，2 例；CISGEM 组，1 例）。结论 mFOLFIRINOX 三联化疗未达到主要研究终点。 CISGEM 双药化疗仍然是晚期 BTC 的一线标准。
PURPOSE Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown. METHODS In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate >= 59%, 73% expected). RESULTS A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events >= grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one). CONCLUSION mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.