METHODS: In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).
RESULTS: Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.
CONCLUSIONS: The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.
方法:在这项随机II期试验中,患者被分配(3∶2)至二线P-FOLFIRI组(A组)或单用FOLFIRI组(B组).在研究开始和疾病进展时收集用于循环肿瘤DNA分析的LB。主要终点为6个月无进展生存期。两阶段西蒙设计需要纳入85例患者(EudraCT2017-004519-38)。
结果:在2019年2月至2020年11月之间,对49例患者进行了筛查(在LB中检测到16例RAS突变),其中31例患者(18例分配给A组,13例分配给B组)。由于招聘不足,该研究过早结束。A组的严重不良事件发生率更高(44%vs.23%)。总反应率为33%(A组)与7.7%(B臂)。6个月无进展生存率分别为66.7%(A组)和38.5%(B组)。中位无进展生存期为11.0个月(A组)和4.0个月(B组)(风险比,0.58)。在疾病进展时,在A组的4/11例患者(36%)和B组的2/10例患者(20%)中发现了LB中的RAS或BRAF突变。
结论:BEYOND研究表明,在LB选择的WTRAS状态的转移性结直肠癌患者中,P-FOLFIRI除了进展为P-FOLFOX之外,还有意义的益处。这一战略值得进一步研究。