原发肿瘤侧别对转移性结直肠癌的预后和治疗结果有影响：来自两项随机一线帕尼单抗研究的结果。
Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.
机构信息
Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium.
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
出版信息
Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.
BACKGROUND
Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.
MATERIALS AND METHODS
Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.
RESULTS
Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).
CONCLUSION
The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.
TRIAL REGISTRATION (CLINICALTRIALS.GOV): PRIME (NCT00364013), PEAK (NCT00819780).
背景
先前的研究报告了转移性结直肠癌（mCRC）中原发肿瘤侧别对预后的影响及其对西妥昔单抗疗效的影响。本回顾性分析了两项帕尼单抗试验的数据，研究了 RAS 野生型（WT）原发肿瘤的一线 mCRC 患者中肿瘤侧别与治疗效果之间的可能关联。
材料和方法
对两项随机一线帕尼单抗试验的数据进行了分析，按 RAS WT 患者的原发肿瘤侧别评估治疗结局。PRIME（III 期；NCT00364013）比较了帕尼单抗联合 FOLFOX 与 FOLFOX 单药治疗；PEAK（II 期；NCT00819780）比较了帕尼单抗联合 FOLFOX 与贝伐珠单抗联合 FOLFOX。盲肠至横结肠的原发肿瘤被编码为右侧，而从脾曲至直肠的肿瘤被认为是左侧。
结果
肿瘤侧别确定（RAS WT 人群）为 83%（n=559/675）；78%（n=435）的患者为左侧肿瘤，22%（n=124）为右侧肿瘤。在 RAS WT 人群和 RAS/BRAF WT 亚组中，右侧肿瘤患者的所有疗效参数均较左侧肿瘤患者差。在左侧肿瘤患者中，帕尼单抗治疗的结局优于对照组，包括中位总生存期（PRIME：30.3 与 23.6 个月，调整后的危险比=0.73，P=0.0112；PEAK：43.4 与 32.0 个月，调整后的危险比=0.77，P=0.3125）。
结论
这些回顾性分析的结果证实，在 RAS WT 患者中，右侧原发肿瘤的预后较左侧肿瘤差，而与一线治疗无关。与单独化疗或联合贝伐珠单抗相比，RAS WT 患者左侧肿瘤接受帕尼单抗治疗获益更大，包括总生存优势（治疗差异：PRIME 6.7 个月；PEAK 11.4 个月）。由于右侧 mCRC 的 RAS WT 患者数量相对较少，因此无法对其最佳治疗方法得出最终结论。需要在该领域进行进一步的研究。
试验注册（ClinicalTrials.gov）：PRIME（NCT00364013），PEAK（NCT00819780）。
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