Gorka Eszter, Fabó Dániel, Gézsi András, Czirbesz Kata, Fedorcsák Imre, Liszkay Gabriella
Dermatooncology Department, National Institute of Oncology, Ráth György str. 7-9, Budapest, H-1122, Hungary.
Epilepsy Centrum, Department of Neurology, National Institute of Clinical Neurosciences, Amerikai str. 57, Budapest, H-1145, Hungary.
Pathol Oncol Res. 2018 Apr;24(2):401-406. doi: 10.1007/s12253-017-0256-9. Epub 2017 Jun 1.
Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0-2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0-2 treated with local therapies and/or chemotherapy, between 2003 and 2015. We found the intracranial disease control rate (DCR) was 83% including four (13%) complete remissions (CR), nine (30%) partial remissions (PR) and twelve (40%) stable diseases (SD) in contrast to five (17%) progressive diseases (PD). With a median follow-up of 14 months, median progression-free survival (PFS) and overall survival (OS) were 5.5 months, and 8.8 months, respectively. If calculated from BM onset, the OS turned to be 11.8 months on the dabrafenib arm, while it was only 6.0 months in the control arm (HR = 0.45, p = 0.0014). Higher risk of progression was observed with increasing ECOG (HR =4.06, p = 0.00027) and if more than 2 extracranial organs were involved (HR = 3.4, p = 0.0077). Elevated lactate dehydrogenase (LDH) was non-significantly associated with worse clinical outcome. Remarkable intracranial activity of dabrafenib in real practice was confirmed by our analysis.
达拉非尼是一种有效的BRAF抑制剂，具有颅内肿瘤活性。我们进行回顾性分析的目的是评估达拉非尼对黑色素瘤脑转移（BM）患者的疗效。我们研究了30例BRAF突变的黑色素瘤BM患者，他们在2014年至2017年间脑部得到局部控制后接受了达拉非尼治疗。东部肿瘤协作组体能状态（ECOG）为0 - 2。对照组由204例来自我们机构黑色素瘤数据库的黑色素瘤患者组成，这些患者有BM且ECOG为0 - 2，在2003年至2015年间接受了局部治疗和/或化疗。我们发现颅内疾病控制率（DCR）为83%，包括4例（13%）完全缓解（CR）、9例（30%）部分缓解（PR）和12例（40%）病情稳定（SD），相比之下有5例（17%）疾病进展（PD）。中位随访14个月时，中位无进展生存期（PFS）和总生存期（OS）分别为5.5个月和8.8个月。如果从BM发病开始计算，达拉非尼治疗组的OS为11.8个月，而对照组仅为6.0个月（HR = 0.45，p = 0.0014）。随着ECOG升高（HR = 4.06，p = 0.00027）以及如果有超过2个颅外器官受累（HR = 3.4，p = 0.0077），观察到疾病进展风险更高。乳酸脱氢酶（LDH）升高与较差的临床结局无显著相关性。我们的分析证实了达拉非尼在实际应用中具有显著的颅内活性。
