Cremolini Chiara, Pietrantonio Filippo, Tomasello Gianluca, Dadduzio Vincenzo, Moretto Roberto, Morano Federica, Schirripa Marta, Antoniotti Carlotta, Fucà Giovanni, Bergamo Francesca, Rossini Daniele, Nichetti Federico, Ziampiri Stamatia, Ghidini Michele, Marmorino Federica, Prisciandaro Michele, Falcone Alfredo, De Braud Filippo, Loupakis Fotios, Lonardi Sara
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
ESMO Open. 2017 Aug 10;2(3):e000241. doi: 10.1136/esmoopen-2017-000241. eCollection 2017.
BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on mutated and -like CRC models. We designed a phase II trial to test the activity of vinorelbine in patients with BRAF V600E mutated metastatic CRC (mCRC).
Patients progressed to or not deemed eligible for standard treatments received oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21 days. Primary endpoint was objective response rate (ORR).
Twenty patients were enrolled; 75% of them were highly pretreated. No responses were observed (0%); only one patient had a confirmed disease stabilisation (5%). Median progression-free survival was 1 month (95% CI 0.8 to 1.8), median overall survival was 2.1 months (95% CI 1.6 to 3.7). No serious adverse events were observed.
Despite encouraging preclinical data, our study did not show signs of clinical activity for vinorelbine in this patients' population. Further investigations on molecular heterogeneity and dynamic evolution of BRAF V600E mutated mCRC are needed.
BRAF V600E突变定义了一个预后较差的特定结直肠癌（CRC）亚组。有前景的临床前数据显示，有丝分裂纺锤体毒素在突变型及类似CRC模型上具有合成致死活性。我们设计了一项II期试验，以测试长春瑞滨对BRAF V600E突变的转移性结直肠癌（mCRC）患者的活性。
病情进展或被认为不符合标准治疗条件的患者，每21天的第1天和第8天接受口服（60mg/平方米）或静脉注射（25mg/平方米）长春瑞滨治疗。主要终点是客观缓解率（ORR）。
入组20例患者；其中75%接受过高度预处理。未观察到缓解（0%）；仅1例患者疾病得到确认稳定（5%）。无进展生存期的中位数为1个月（95%CI 0.8至1.8），总生存期的中位数为2.1个月（95%CI 1.6至3.7）。未观察到严重不良事件。
尽管临床前数据令人鼓舞，但我们的研究未显示长春瑞滨在该患者群体中的临床活性迹象。需要对BRAF V600E突变的mCRC的分子异质性和动态演变进行进一步研究。
