FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109)
FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109)
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DOI：
10.1200/jco.19.01340
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发表时间：
2019-12-10
影响因子：
45.3
通讯作者：
Geissler, Michael
中科院分区：
文献类型：
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作者：
Modest, Dominik P.;Martens, Uwe M.;Geissler, Michael
目的本试验研究帕尼单抗加氟尿嘧啶/亚叶酸、奥沙利铂和伊立替康三联化疗（FOLFOXIRI）在未经治疗的RAS野生型（WT）转移性结直肠癌患者中的2：1随机、对照、开放标签、II期临床试验。如果ORR>= 75%，则认为实验组（改良FOLFOXIRI [mFOLFOXIRI]+帕尼单抗）具有活性。将实验ORR与基于历史数据的估计ORR 60%进行比较，并通过随机对照组（FOLFOXIRI）进行验证。该试验的功效为80%，潜在I类错误为0.05。次要终点包括二次切除率、毒性反应、无进展生存期和总生存期。结果63例患者被随机分配到试验组，33例患者被随机分配到对照组，mFOLFOXIRI联合帕尼单抗组的ORR超过75%，与FOLFOXIRI相比更高（87.3%对60.6%;比值比，4.469; 95% CI，1.61至12.38; P = .004）。在添加帕尼单抗后，二次切除率有所改善（33.3% vs 12.1%; P = 0.02）。研究组的无进展生存期相似，而总生存期显示出有利于含帕尼单抗组的趋势（死亡风险比，0.67; 95% CI，0.41至1.11; P = 0.12）结论：在RAS WT转移性结直肠癌患者中，在mFOLFOXIRI基础上添加帕尼单抗可改善ORR和转移灶的二次切除率，选择需要高活性一线治疗的选定和合适患者。未来的研究应确定在mFOLFOXIRI基础上增加帕尼单抗是否会延长生存期。
PURPOSE This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.PATIENTS AND METHODS The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was >= 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival.RESULTS A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12).CONCLUSION The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.