Rivera Fernando, Karthaus Meinolf, Hecht J Randolph, Sevilla Isabel, Forget Frédéric, Fasola Gianpiero, Canon Jean-Luc, Guan Xuesong, Demonty Gaston, Schwartzberg Lee S
Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla, 39008, Santander, Spain.
Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany.
Int J Colorectal Dis. 2017 Aug;32(8):1179-1190. doi: 10.1007/s00384-017-2800-1. Epub 2017 Apr 19.
To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).
Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).
One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.
First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.
报告II期PEAK试验（NCT00819780）计划的最终总生存期（OS）和无进展生存期（PFS）分析。
既往未经治疗、KRAS外显子2野生型（WT）转移性结直肠癌（mCRC）患者被随机分为mFOLFOX6联合帕尼单抗或贝伐单抗组。主要终点为PFS；次要终点包括OS、客观缓解率、缓解持续时间（DoR）、缓解时间、切除率和安全性。按肿瘤RAS状态的治疗效果是一个预先设定的目标。探索性分析包括早期肿瘤缩小（ETS）和缓解深度（DpR）。
170例患者为RAS WT，156例为RAS WT/BRAF WT mCRC。在RAS WT人群中，帕尼单抗组的中位PFS长于贝伐单抗组（12.8个月对10.1个月；风险比（HR）=0.68[95%置信区间（CI）=0.48 - 0.96]；p = 0.029），在RAS WT/BRAF WT人群中也是如此（13.1个月对10.1个月；HR = 0.61[95%CI = 0.42 - 0.88]；p = 0.0075）。在RAS WT人群中，帕尼单抗组与贝伐单抗组的中位OS（68%的OS事件）分别为36.9个月对28.9个月（HR = 0.76[95%CI = 0.53 - 1.11]；p = 0.15），在RAS WT/BRAF WT人群中分别为41.3个月对28.9个月（HR = 0.70[95%CI = 0.48 - 1.04]；p = 0.08）。帕尼单抗组的中位DoR（11.4个月对9.0个月；HR = 0.59[95%CI = 0.39 - 0.88]；p = 0.011）和DpR（65.0%对46.3%；p = 0.0018）得到改善。更多帕尼单抗组患者在第8周经历了≥30%的ETS（64%对45%；p = 0.052）；ETS与改善的PFS/OS相关。未出现新的安全信号。
对于RAS WT mCRC患者，一线帕尼单抗 + mFOLFOX6较贝伐单抗 + mFOLFOX6可提高PFS。
