Pietrantonio Filippo, Maggi Claudia, Di Bartolomeo Maria, Facciorusso Maria Grazia, Perrone Federica, Testi Adele, Iacovelli Roberto, Miceli Rosalba, Bossi Ilaria, Leone Giorgia, Milione Massimo, Pelosi Giuseppe, de Braud Filippo
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
PLoS One. 2014 Apr 1;9(4):e92147. doi: 10.1371/journal.pone.0092147. eCollection 2014.
Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations.
We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number--defined as mean of 3 to 5 fusion signals in ≥ 10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease.
No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885).
Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.
尽管西妥昔单抗和帕尼单抗对KRAS-NRAS-BRAF和PI3KCA野生型转移性结直肠癌患者显示出更高的疗效，但在分子富集人群的一个相关亚组中会出现原发性耐药。
我们根据ALK基因状态（二体性与ALK基因拷贝数增加，定义为≥10%的细胞中3至5个融合信号的平均值）评估了68例晚期结直肠癌患者的RAS、BRAF和PI3KCA状态。所有连续的患者均接受西妥昔单抗和伊立替康或单独使用帕尼单抗治疗难治性化疗疾病。
未检测到ALK易位或扩增。在25例（37%）肿瘤中发现ALK基因拷贝数增加。与基因拷贝数增加的患者相比，二体性ALK患者的缓解率显著更高（70%对32%；p = 0.0048）。同样，两组比较时无进展生存期也有显著差异（6.7对5.3个月；p = 0.045）。总生存期也观察到一种趋势（18.5对15.6个月；p = 0.885）。
ALK基因拷贝数增加可能是转移性结直肠癌的一个不良预后因素，并且可能在抗表皮生长因子受体治疗耐药中起作用。
