贝伐珠单抗或贝伐珠单抗联合节拍化疗作为转移性结直肠癌一线诱导治疗后维持治疗的 II 期随机研究：MOMA 试验
Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial.
机构信息
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology - IRCCS, Padova, Italy.
出版信息
Eur J Cancer. 2019 Mar;109:175-182. doi: 10.1016/j.ejca.2018.12.028. Epub 2019 Feb 5.
BACKGROUND
Alternating induction and maintenance phases is a common strategy in metastatic colorectal cancer (mCRC). Metronomic chemotherapy (metroCT) may represent a well-tolerated chemotherapy backbone for maximising bevacizumab effect during maintenance. The MOMA trial was designed to compare metroCT plus bevacizumab versus bevacizumab alone as maintenance following 4 months of induction with FOLFOXIRI plus bevacizumab.
PATIENTS AND METHODS
In this phase II study, patients with unresectable mCRC were randomised to receive up to 8 cycles of FOLFOXIRI plus bevacizumab, followed by bevacizumab (arm A) or the same regimen followed by bevacizumab plus metroCT (capecitabine 500 mg/three times per day and cyclophosphamide 50 mg/die, arm B) until disease progression. The primary end-point was progression-free survival (PFS). According to the Rubinstein and Korn's design, to detect a hazard ratio[HR] of 0.75 favouring arm B, with 1 sided-alpha and beta errors of 15% and 80%, 173 events and 222 patients were required.
RESULTS
Between May 2012 and March 2015, 232 patients, mostly with RAS (65%) or BRAF (9%) mutant tumours, were randomised in 16 Italian centres. At a median follow-up of 47.8 months, 210 and 164 progression and death events were registered. The primary end-point was not met. Median PFS was 10.3 and 9.4 months in arm B and A, respectively (HR: 0.94 [70% confidence interval {CI}: 0.82-1.09], p = 0.680). No significant differences were reported in terms of overall survival (OS) (median OS arm B/A: 22.5/28 months; HR: 1.16 [95%CI: 0.99-1.37], p = 0.336). Response rate with FOLFOXIRI plus bevacizumab was 63% (arm B/A: 58%/68%). In the liver-limited subgroup, the secondary resection rate was 49% (arm B/A: 45%/55%).
CONCLUSIONS
The addition of metroCT to maintenance with bevacizumab does not significantly improve PFS of mCRC patients. The activity of FOLFOXIRI plus bevacizumab is confirmed in a population with high prevalence of RAS/BRAF mutations treated with a 4-months induction.
TRIAL REGISTRATION
www.clinicaltrials.gov NCT02271464.
背景
在转移性结直肠癌（mCRC）中，交替诱导和维持阶段是一种常见的策略。节拍化疗（metroCT）可能代表一种耐受良好的化疗骨干，可在维持期间最大限度地提高贝伐珠单抗的效果。MOMA 试验旨在比较 metroCT 加贝伐珠单抗与贝伐珠单抗单独维持治疗 4 个月 FOLFOXIRI 加贝伐珠单抗后的疗效。
患者和方法
在这项 II 期研究中，不可切除的 mCRC 患者被随机分配接受最多 8 个周期的 FOLFOXIRI 加贝伐珠单抗，然后接受贝伐珠单抗（A 组）或相同方案加贝伐珠单抗加 metroCT（卡培他滨 500 mg/每天 3 次和环磷酰胺 50 mg/每天），直到疾病进展。主要终点是无进展生存期（PFS）。根据鲁宾斯坦和科恩的设计，要检测到有利于 B 组的风险比[HR]为 0.75，单侧α和β错误分别为 15%和 80%，需要 173 个事件和 222 名患者。
结果
2012 年 5 月至 2015 年 3 月，16 家意大利中心的 232 名患者主要为 RAS（65%）或 BRAF（9%）突变肿瘤患者被随机分配。中位随访 47.8 个月时，记录到 210 和 164 例进展和死亡事件。主要终点未达到。B 组和 A 组的中位 PFS 分别为 10.3 和 9.4 个月（HR：0.94[70%置信区间：0.82-1.09]，p=0.680）。在总生存期（OS）方面，未报告显著差异（中位 OS 组 B/A：22.5/28 个月；HR：1.16[95%CI：0.99-1.37]，p=0.336）。FOLFOXIRI 加贝伐珠单抗的缓解率为 63%（组 B/A：58%/68%）。在肝局限性亚组中，二次切除术率为 49%（组 B/A：45%/55%）。
结论
在贝伐珠单抗维持治疗中添加 metroCT 并不能显著改善 mCRC 患者的 PFS。FOLFOXIRI 加贝伐珠单抗的活性在 RAS/BRAF 突变率较高的人群中得到证实，这些患者接受了 4 个月的诱导治疗。
试验注册
www.clinicaltrials.gov NCT02271464。
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