Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT trial embedded phase II population.

In this article, we present results of the embedded randomised phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in RAS and BRAF-wild-type (wt) patients and with biomarker hyperselection.

在这篇文章中，我们展示了嵌入式随机 II 期试验的结果，该试验测试了在 RAS 和 BRAF 野生型（wt）患者中将帕尼单抗添加到新辅助 FOLFOX 与仅使用 FOLFOX 的比较，并进行了生物标志物超选择。

patients_and_methods

Patients had operable, computed tomography-predicted stage T3-4, N0-2, M0 colon adenocarcinoma.

患者患有可手术的、计算机断层扫描预测的T3-4期、N0-2期、M0期结肠腺癌。

KRAS-wt patients allocated to NAC could optionally be sub-randomised 1 : 1 to FOLFOX ± panitumumab during the preoperative phase.

KRAS野生型患者在术前阶段被分配接受新辅助化疗(NAC)时，可以选择1:1随机分配接受FOLFOX±帕尼单抗。

RAS/BRAF were tested by next-generation sequencing; and epiregulin (EREG)/amphiregulin (AREG) by RNAseq.

RAS/BRAF通过下一代测序技术进行检测；而表皮调节素(EREG)/双调蛋白(AREG)则通过RNA测序进行检测。

The primary endpoint was time to recurrence (TTR) in RAS/BRAF-wt patients; secondary endpoints included safety, histological down-staging, disease-free survival (DFS), colon cancer-specific survival (CCSS), overall survival(OS) and impact of primary tumour location and EREG/AREG.

主要终点是RAS/BRAF野生型患者的复发时间(TTR)；次要终点包括安全性、组织学降级、无病生存期(DFS)、结肠癌特异性生存期(CCSS)、总生存期(OS)以及原发肿瘤位置和EREG/AREG的影响。

Results

In total 269 KRAS-wt patients were enrolled into the embedded phase II trial. Extended RAS/BRAF data were available for 232 (83%) patients; 22/232 (9.5%) were RAS-mutant; 41/210 (20%) were BRAF-mutant.

共有269名KRAS野生型患者被纳入嵌入式II期试验。有232名（83%）患者的扩展RAS/BRAF数据可用；其中22/232（9.5%）为RAS突变型；41/210（20%）为BRAF突变型。

Median follow-up was 42 months.

中位随访时间为42个月。

In 169 RAS/BRAF-wt patients, there was a trend towards reduced recurrences with FOLFOX plus panitumumab compared with FOLFOX (12% versus 21%, hazard ratio= 0.51, P = 0.09); significant improvements were seen for DFS, CCSS and OS.

在169名RAS/BRAF野生型患者中，与仅使用FOLFOX方案相比，FOLFOX联合帕尼单抗治疗复发率有降低趋势（12%对比21%，风险比=0.51，P=0.09）；疾病无进展生存期（DFS）、癌症特异性生存期（CCSS）和总生存（OS）有显著改善。

Within the hyperselected EREG/AREG-high group, there was significant reduction in recurrences with panitumumab.

在高度筛选的EREG/AREG高表达组中，使用帕尼单抗治疗复发率显著降低。

Panitumumab was not associated with increased pathological regression of the primary tumour (tumour regression grade 1-3 16% versus 22%, P = 0.27).

帕尼单抗并未与原发肿瘤的病理退缩增加相关（肿瘤退缩分级1-3为16%对比22%，P=0.27）

FOLFOX plus panitumumab was associated with higher rates of grade 3 diarrhoea (8% versus 3%) and rash (22% versus 2%).

FOLFOX联合帕尼单抗与更高的3级腹泻（8%对比3%）和皮疹（22%对比2%）发生率相关

Conclusions

This exploratory analysis from a randomised phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to perioperative FOLFOX in RAS/BRAF-wt LACC.

这项来自随机化II期研究的探索性分析显示，在RAS/BRAF野生型局部晚期宫颈癌（LACC）中，新辅助帕尼单抗联合围手术期FOLFOX治疗相较于单纯围手术期FOLFOX治疗，无进展生存期（TTR）有非显著性改善。

Hyperselection with EREG/AREG status was associated with increased efficacy.

通过EREG/AREG状态进行的超选择与疗效增加相关。

A dedicated prospective trial within a biomarker-selected population is under development.

正在开发一项针对生物标志物筛选人群的专门前瞻性试验。