PDF(Pubmed)
Abstract：
OBJECTIVE: Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).
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.
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.
摘要：
目的：帕尼单抗联合FOLFOX（P-FOLFOX）是RAS野生型（WT）转移性结直肠癌的标准一线治疗方案。帕尼单抗再激发的价值目前未知。我们评估了在液体活检（LB）中无RAS突变的患者中，将帕尼单抗添加到FOLFIRI（P-FOLFIRI）后进展为P-FOLFOX。
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。
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。
