Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
J Natl Cancer Inst. 2014 Jun 23;106(7). doi: 10.1093/jnci/dju121. Print 2014 Jul.
In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.
在这项对 EXPERT-C 试验的更新分析中，我们表明，在磁共振成像定义的高危局部进展期直肠癌中，在新辅助 CAPOX 治疗方案的基础上添加西妥昔单抗，然后进行放化疗、手术和辅助 CAPOX，无论 KRAS/BRAF 野生型还是未选择的患者，均不能显著提高无进展生存期（PFS）和总生存期（OS）。在回顾性生物标志物分析中，TP53 没有预后价值，但作为西妥昔单抗获益的独立预测生物标志物出现。中位随访 65.0 个月后，接受西妥昔单抗治疗的 TP53 野生型患者（n = 69）的 PFS 有显著改善（5 年时分别为 89.3%和 65.0%；风险比 [HR] = 0.23；95%置信区间 [CI] = 0.07 至 0.78；双侧 P =.02 采用 Cox 回归）和 OS（5 年时分别为 92.7%和 67.5%；HR = 0.16；95%CI = 0.04 至 0.70；双侧 P =.02 采用 Cox 回归）明显优于接受对照治疗的 TP53 野生型患者。发现了 TP53 状态和西妥昔单抗作用之间的相互作用（P <.05），并且在调整了统计学上显著的预后因素和 KRAS 后仍然具有统计学意义。
