Institut Sainte-Catherine, Avignon, France.
Lacassagne Anticancer Center, Nice, France.
PLoS One. 2020 Dec 21;15(12):e0243997. doi: 10.1371/journal.pone.0243997. eCollection 2020.
Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC.
PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety.
A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies.
ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.
西妥昔单抗可改善 KRAS 野生型（wt）转移性结直肠癌（mCRC）患者的无进展生存期（PFS）和总生存期（OS）。关于影响西妥昔单抗治疗疗效和依从性的因素的数据很少，西妥昔单抗联合化疗是 KRAS wt mCRC 患者的标准一线治疗方案。
PREMIUM 是一项前瞻性、法国多中心、观察性研究，于 2009 年 10 月 28 日至 2012 年 4 月 5 日期间招募了计划接受西妥昔单抗治疗（联合或不联合一线化疗）的 KRAS wt mCRC 患者，这些患者均来自于常规临床实践（ClinicalTrials.gov 标识符：NCT01756625）。主要终点是影响西妥昔单抗治疗疗效和依从性的因素。预设的疗效终点是 PFS 和安全性。
共 94 名医生招募了 493 名患者。中位随访时间为 12.9 个月。中位无进展生存期为 11 个月[9.6-12]。单因素分析显示，ECOG 表现状态（PS）、吸烟状态、原发肿瘤部位、转移性器官数量、转移灶可切除性、手术、滤泡炎、皮肤干燥和甲床炎的最大分级以及痤疮预防性治疗有统计学意义。多因素分析（多变量逐步 Cox 模型的风险比）显示，ECOG PS、手术、皮肤干燥和滤泡炎是预测 PFS 延长的阳性预后因素。所有患者中，有 69 名（14%）为非依从性患者。多因素分析显示，无变量具有统计学意义。西妥昔单抗的安全性与之前的研究一致。
ECOG PS<2、进行手术治疗以及出现最大分级的皮肤干燥或滤泡炎是预测 KRAS wt mCRC 患者西妥昔单抗疗效的因素。遗憾的是，我们未能确定这些患者依从性的预测因素。
