Brodowicz Thomas, Liegl-Atzwanger Bernadette, Penel Nicolas, Mir Olivier, Blay Jean-Yves, Kashofer Karl, Le Cesne Axel, Decoupigny Emilie, Wallet Jennifer, Hamacher Rainer, Deley Marie-Cécile Le
Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna-General Hospital, 1090 Vienna, Austria.
Diagnostic and Research Institute of Pathology, Comprehensive Cancer Center, Subunit Sarcoma, Medical University of Graz, 8036 Graz, Austria.
Cancers (Basel). 2020 Dec 12;12(12):3746. doi: 10.3390/cancers12123746.
Regorafenib significantly prolonged progression-free survival (PFS) in pretreated patients with advanced non-adipocytic sarcoma (HR = 0.46; < 0.001) in a placebo-controlled, randomized, phase-II trial (NCT01900743). Thus, here, we assessed the prevalence of 57 biomarkers and their prognostic and predictive values for PFS and overall survival (OS). We analyzed 134/182 patients included in this trial, treated with regorafenib ( = 71, 53%) or placebo ( = 63, 47%). Mutational analyses were performed via full coding sequence analysis for 10 genes, and mutation hotspot panel for 50 genes (four genes in common). H19 was studied with RNA in-situ hybridization. The prognostic and predictive biomarkers' values were studied only for biomarkers found positive/mutated in at least 10 patients. Overall, 25 out of 57 studied biomarkers, including five out of seven genes involved in angiogenesis, were found mutated/positive in at least one patient, of which 23 biomarkers had low prevalence (fewer than eight out of 134 patients), contrasting with H19 ( = 24, 18%), and TP53 ( = 35, 26%). However, in multivariable models of PFS and OS, including treatment effects and interactions, no significant prognostic or predictive values of the tested biomarkers were observed. Though several promising biomarkers were found to be positive/mutated, none of them were identified as viable predictive and prognostic biomarkers.
在一项安慰剂对照、随机、II期试验（NCT01900743）中，瑞戈非尼显著延长了晚期非脂肪细胞肉瘤预处理患者的无进展生存期（PFS）（HR = 0.46；P < 0.001）。因此，在此我们评估了57种生物标志物的患病率及其对PFS和总生存期（OS）的预后和预测价值。我们分析了该试验中纳入的134/182例患者，这些患者接受了瑞戈非尼治疗（n = 71，53%）或安慰剂治疗（n = 63，47%）。通过对10个基因进行全编码序列分析以及对50个基因（有4个基因相同）进行突变热点分析来进行突变分析。采用RNA原位杂交研究H19。仅对在至少10例患者中发现为阳性/突变的生物标志物研究其预后和预测生物标志物价值。总体而言，在57种研究的生物标志物中，有25种在至少1例患者中发现突变/阳性，其中包括7种参与血管生成的基因中的5种，其中23种生物标志物患病率较低（134例患者中少于8例），这与H19（n = 24，18%）和TP53（n = 35，26%）形成对比。然而，在包括治疗效果和相互作用的PFS和OS多变量模型中，未观察到所测试生物标志物的显著预后或预测价值。尽管发现了几种有前景的生物标志物为阳性/突变，但它们均未被确定为可行的预测和预后生物标志物。
