PDF(Pubmed)
Abstract：
Background: The combination therapy of BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been approved as a first-line treatment for metastatic melanoma with BRAF V600 mutants. Recently, BRAF mutations have been divided into three subtypes based on biochemical and signaling characteristics. Unlike V600 mutants that show class I BRAF mutations, evidence of the effects of using BRAF inhibitors and MEK inhibitors in patients with non-V600 BRAF mutations remains unclear. The exploration of effective therapy for non-V600 BRAF mutations in melanoma has thus attracted much interest. Case presentation: We reported a case of a 64-year-old female metastatic melanoma patient with a novel BRAF p.L485-P490 deletion mutation. The patient received anti-PD1 agent pembrolizumab (100 mg) therapy as the first-line treatment for two cycles, which was terminated due to an intolerable adverse effect. Considering the p.L485-P490 deletion mutation signal as an active dimer which is akin to a class II BRAF mutation, the patient underwent dabrafenib and trametinib combination therapy as a second-line treatment. After two cycles of combination treatment, the patient achieved a partial response confirmed by radiological examinations. At the last follow-up date, the patient had obtained over 18 months of progression-free survival, and the treatment was well tolerated. Conclusion: The combination therapy of dabrafenib and trametinib has been proven to be an effective method as a later-line therapy for metastatic melanoma patients with class II BRAF in-frame deletion mutations.
摘要：
背景：BRAF抑制剂（BRAFis）和MEK抑制剂（MEKis）的联合治疗已被批准为BRAFV600突变体转移性黑色素瘤的一线治疗。最近,BRAF突变已根据生化和信号特征分为三种亚型。与显示I类BRAF突变的V600突变体不同，在非V600BRAF突变患者中使用BRAF抑制剂和MEK抑制剂的效果的证据尚不清楚.因此，探索黑素瘤中非V600BRAF突变的有效疗法吸引了很多兴趣。病例介绍：我们报道了一例64岁的女性转移性黑色素瘤患者，患者有一个新的BRAFp.L485-P490缺失突变。患者接受抗PD1药物pembrolizumab（100mg）作为一线治疗两个周期，由于难以忍受的不利影响而终止。考虑p.L485-P490缺失突变信号作为类似于II类BRAF突变的活性二聚体，患者接受了dabrafenib和曲美替尼联合治疗作为二线治疗.经过两个周期的联合治疗，患者通过放射学检查得到部分缓解.在最后一次随访日期，患者获得了超过18个月的无进展生存期，治疗耐受性良好。结论：dabrafenib和trametinib的联合治疗已被证明是一种有效的方法，可以作为具有II类BRAF框内缺失突变的转移性黑色素瘤患者的后期治疗方法。
