Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 2168511, Japan.
Department of Clinical Oncology, Kagawa University Faculty of Medicine Cancer Center, Kagawa University Hospital, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Target Oncol. 2017 Dec;12(6):787-794. doi: 10.1007/s11523-017-0527-0.
The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab.
We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment.
Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman's rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study.
Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (r = 0.56, P < 0.0001; r = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (r = 0.56, P < 0.0001), as well as OS (r = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (r = 0.44, P < 0.0001).
Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022).
在转移性结直肠癌（mCRC）患者中，与贝伐珠单抗相比，西妥昔单抗治疗导致癌胚抗原（CEA）水平更快、更大幅度的下降，与生存延长相关，这些患者接受西妥昔单抗治疗。
我们研究了 CEA 值的变化程度是否可以作为预测 mCRC 患者接受西妥昔单抗联合方案一线治疗时生存和肿瘤退缩的诊断工具。
在两项一线治疗的 II 期试验中（JACCRO CC-05 试验中使用西妥昔单抗联合 FOLFOX 和 CC-06 试验中使用西妥昔单抗联合 SOX），对 113 例 mCRC 患者的 CEA 下降、深度缓解（DpR）和临床结局之间的关系进行了评估。使用 Spearman 秩相关系数进行分析。以 CEA 降低 75%作为截断值，根据之前的研究结果定义 CEA 反应，并基于 CEA 反应区分 CEA 应答者。
92 例患者有资格同时进行 CEA 和 DpR 分析。CEA 降低的中位数为 67.4%，CEA 最低点的中位时间为 2.8 个月，与 DpR 的中位时间 3.0 个月相似。DpR 与 PFS 和 OS 相关（r=0.56，P<0.0001；r=0.39，P=0.0090）；此外，CEA 降低与 PFS（r=0.56，P<0.0001）和 OS（r=0.35，P=0.019）相关。CEA 应答者的 PFS 明显更长（11.8 个月 vs. 5.5 个月，风险比 [HR]0.46，P=0.0009），OS 略有延长，但无统计学意义（36.2 个月 vs. 23.5 个月；HR 0.57；P=0.072），而 CEA 无应答者。CEA 降低与 DpR 具有统计学显著相关性（r=0.44，P<0.0001）。
本研究表明，DpR 和 CEA 反应均与西妥昔单抗一线治疗的临床结局相关。在接受一线西妥昔单抗治疗的患者中，CEA 降低可能是 DpR 的替代指标（UMIN000004197，UMIN000007022）。
