Sartore-Bianchi Andrea, Moroni Mauro, Veronese Silvio, Carnaghi Carlo, Bajetta Emilio, Luppi Gabriele, Sobrero Alberto, Barone Carlo, Cascinu Stefano, Colucci Giuseppe, Cortesi Enrico, Nichelatti Michele, Gambacorta Marcello, Siena Salvatore
Divisione Oncologia Falck, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
J Clin Oncol. 2007 Aug 1;25(22):3238-45. doi: 10.1200/JCO.2007.11.5956.
In a previous cohort study, we proposed that responsiveness of metastatic colorectal cancer (mCRC) to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies has a genetic basis, being associated with increased EGFR gene copy number (GCN) as measured by fluorescence in situ hybridization (FISH) in individual tumors. The present study was aimed at assessing the predictive role of EGFR GCN, in terms of clinical outcome, in patients treated with panitumumab.
Patients with mCRC refractory to standard therapies were a subset of patients from a phase III trial of panitumumab plus best supportive care (BSC; n = 58) versus BSC alone (n = 34) who were selected on the basis of availability of tumor samples adequate for FISH.
In patients treated with panitumumab, a mean EGFR GCN of less than 2.5/nucleus or less than 40% of tumor cells displaying chromosome 7 polysomy within the tumor predicted for shorter progression-free survival (PFS; P = .039 and P = .029, respectively) and overall survival (P = .015 and P = .014, respectively). None of the treated patients with mean EGFR GCN of less than 2.47/nucleus or less than 43% of tumor cells displaying chromosome 7 polysomy obtained objective response compared with six of 20 and six of 19 patients with values greater than these cutoff limits, respectively (P = .0009 and P = .0007, respectively). Evaluation of BSC-treated patients showed no correlation between EGFR GCN or chromosome 7 polysomy status and PFS.
In a larger and more homogeneous series than in previous studies, present exploratory data suggest that mCRC patients with tumors distinguishable by FISH analysis of EGFR as homogenously disomic or with low chromosome 7 polysomy have a reduced likelihood of response to panitumumab.
在之前的一项队列研究中，我们提出转移性结直肠癌（mCRC）对抗表皮生长因子受体（EGFR）单克隆抗体的反应具有遗传基础，与通过荧光原位杂交（FISH）检测的单个肿瘤中EGFR基因拷贝数（GCN）增加有关。本研究旨在评估EGFR GCN在接受帕尼单抗治疗的患者临床结局方面的预测作用。
对标准治疗难治的mCRC患者是一项帕尼单抗联合最佳支持治疗（BSC；n = 58）与单纯BSC（n = 34）的III期试验患者的一个子集，这些患者是根据有足够用于FISH分析的肿瘤样本而入选的。
在接受帕尼单抗治疗的患者中，肿瘤细胞核平均EGFR GCN小于2.5或肿瘤内显示7号染色体多体性的肿瘤细胞少于40%，预示着无进展生存期（PFS）较短（分别为P = 0.039和P = 0.029）以及总生存期较短（分别为P = 0.015和P = 0.014）。与平均EGFR GCN小于2.47/细胞核或显示7号染色体多体性的肿瘤细胞少于43%的治疗患者相比，没有患者获得客观缓解，而EGFR GCN值大于这些临界值的20例患者中有6例、19例患者中有6例获得客观缓解（分别为P = 0.0009和P = 0.0007）。对接受BSC治疗患者的评估显示，EGFR GCN或7号染色体多体性状态与PFS之间无相关性。
与之前的研究相比，在一个更大且更同质的系列研究中，目前的探索性数据表明，通过FISH分析EGFR可区分的肿瘤为均匀二体或7号染色体多体性低的mCRC患者对帕尼单抗的反应可能性降低。
