QUATTRO-II 随机试验：CAPOXIRI+bevacizumab 对比 FOLFOXIRI+bevacizumab 作为 mCRC 患者一线治疗。
QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC.
机构信息
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Medical Oncology, Kochi Medical School/Kansai Medical University, Nankoku, Japan.
出版信息
Med. 2024 Sep 13;5(9):1164-1177.e3. doi: 10.1016/j.medj.2024.05.012. Epub 2024 Jun 19.
BACKGROUND
The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC).
METHODS
In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes.
FINDINGS
Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%).
CONCLUSION
CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC.
FUNDING
Chugai Pharmaceutical Co., Ltd.
背景
QUATTRO-II 试验评估了卡培他滨+奥沙利铂+伊立替康（CAPOXIRI）+贝伐珠单抗（BEV）与 5-氟尿嘧啶+亚叶酸+奥沙利铂+伊立替康（FOLFOXIRI）+BEV 治疗转移性结直肠癌（mCRC）的疗效和安全性。
方法
这是一项 II 期研究（ClinicalTrials.gov：NCT04097444；jRCTs041190072），患者按 1:1 随机分为 FOLFOXIRI+BEV 或 CAPOXIRI+BEV 组。FOLFOXIRI+BEV/CAPOXIRI+BEV 组的诱导治疗持续 8/6 个周期（如果可行，最多 12/8 个周期），维持治疗为研究者选择的 5-氟尿嘧啶/亚叶酸+BEV 或卡培他滨+BEV。主要终点是无进展生存期（PFS），如果点估计的风险比（HR）为 0.80<HR<1.25，则认为两个臂等效。次要终点是总缓解率（ORR）、总生存期（OS）、不良事件（AE）发生率和患者报告的结局。
结果
共有 51 例和 52 例患者分别随机分配至 FOLFOXIRI+BEV 和 CAPOXIRI+BEV 组。研究达到了主要终点；在中位随访 23.7 个月时，FOLFOXIRI+BEV 臂的 PFS 为 10.6 个月（95%CI，7.7-13.3），CAPOXIRI+BEV 臂为 10.9 个月（95%CI，9.3-14.3）（HR 1.114[0.80<HR<1.25]，p=0.654）。在 FOLFOXIRI+BEV 与 CAPOXIRI+BEV 臂中，2 年 OS 率（95%CI）分别为 65.5%（49.5%-77.6%）和 74.3%（59.8%-84.2%），ORR（95%CI）分别为 76.5%（62.5%-87.2%）和 84.6%（71.9%-93.1%）。FOLFOXIRI+BEV 与 CAPOXIRI+BEV 臂中主要（≥3 级）AE 为中性粒细胞减少（68.6%比 40.4%）、发热性中性粒细胞减少（9.8%比 11.5%）、腹泻（7.8%比 17.3%）和食欲下降（7.8%比 17.3%）。
结论
CAPOXIRI+BEV 耐受性良好，血液学毒性降低，疗效与 FOLFOXIRI+BEV 相当，为 mCRC 患者提供了一种可能更方便的一线治疗选择。
资金来源
中外制药株式会社。
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