Gonzalez-Cao Maria, Boada Aram, Teixidó Cristina, Fernandez-Figueras María Teresa, Mayo Clara, Tresserra Francesc, Bustamante Jean, Viteri Santiago, Puertas Enrique, Santarpia Mariacarmela, Riso Aldo, Barron Feliciano, Karachaliou Niki, Rosell Rafael
Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital-Quirónsalud Group, Barcelona, Spain.
Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Oncotarget. 2016 Aug 30;7(35):56619-56627. doi: 10.18632/oncotarget.10651.
Approximately 50% of metastatic melanoma patients harbor BRAF mutations. Several treatment options including the combination of BRAF and MEK inhibitors (BRAF/MEKi) and immunotherapy (mainly anti CTLA-4 and anti PD-1 antibodies), have been shown to improve survival in these patients. Although preclinical data support the synergistic effect of both modalities in combination, data confirming the activity and tolerability of these combinations are not yet available in the clinical setting. Herein, we report the case of a melanoma patient treated with sequential BRAF/MEKi (dabrafenib plus trametinib) followed by the anti CTLA-4 antibody ipilimumab who achieved a pathological complete response. Unfortunately, the patient died due to fatal gastrointestinal (GI) toxicity. Analysis of the BRAFV600E mutation in circulating tumoral DNA (ctDNA) from peripheral blood samples and serial tumor tissue biopsies throughout treatment demonstrated a good correlation with clinical evolution.
大约50%的转移性黑色素瘤患者存在BRAF突变。包括BRAF和MEK抑制剂联合使用（BRAF/MEKi）以及免疫疗法（主要是抗CTLA-4和抗PD-1抗体）在内的几种治疗方案已被证明可提高这些患者的生存率。尽管临床前数据支持两种治疗方式联合使用的协同效应，但在临床环境中，证实这些联合治疗的活性和耐受性的数据尚未可得。在此，我们报告一例黑色素瘤患者的病例，该患者先接受序贯BRAF/MEKi（达拉非尼加曲美替尼）治疗，随后接受抗CTLA-4抗体伊匹木单抗治疗，达到了病理完全缓解。不幸的是，该患者因致命的胃肠道毒性死亡。在整个治疗过程中，对外周血样本中的循环肿瘤DNA（ctDNA）以及连续的肿瘤组织活检进行BRAFV600E突变分析，结果显示与临床病程具有良好的相关性。
