Center for Oncological Research, University of Antwerp, Wilrijk, Belgium; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Biostatistics, Amgen Ltd, Uxbridge, United Kingdom.
Clin Colorectal Cancer. 2018 Sep;17(3):170-178.e3. doi: 10.1016/j.clcc.2018.03.005. Epub 2018 Mar 8.
The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC.
RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n = 1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecum to transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided.
Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RAS MT patients.
These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors.
原发肿瘤位置对转移性结直肠癌（mCRC）的预后有影响。我们报告了回顾性分析的结果，这些分析评估了肿瘤位置对 RAS 野生型（WT）mCRC 患者二线及以上帕尼单抗治疗的预后和疗效的影响，以及对 RAS 突变型（MT）mCRC 所有治疗线患者预后的影响。
来自两项随机 III 期帕尼单抗试验（ClinicalTrials.gov 标识符，NCT00339183 和 NCT00113763）的 RAS WT 数据（n=483）按肿瘤位置进行分层分析。第二次分析评估了 4 项帕尼单抗研究（ClinicalTrials.gov 标识符，NCT00364013、NCT00819780、NCT00339183 和 NCT00113763）中 RAS MT 患者肿瘤位置的影响（n=1205）。盲肠至横结肠的原发肿瘤被编码为右侧；脾曲至直肠的肿瘤被编码为左侧。
所有患者中，肿瘤位置的确定率为 83%至 88%；71%至 77%的患者有左侧肿瘤。与左侧肿瘤患者相比，RAS WT 右侧肿瘤患者的所有疗效参数均较差。与对照治疗相比，左侧肿瘤患者接受帕尼单抗治疗的效果更好。由于患者数量较少，对于右侧 mCRC 无法得出任何结论。肿瘤位置对 RAS MT 患者生存的预后影响尚不清楚。
这些回顾性分析证实，无论治疗如何，RAS WT 右侧 mCRC 与预后不良相关。RAS WT 左侧肿瘤患者在二线或以后的治疗线中加入帕尼单抗获益。需要进一步研究以确定右侧 mCRC 和 RAS MT 肿瘤的最佳治疗方法。
