Marconcini Riccardo, Galli Luca, Antonuzzo Andrea, Bursi Simona, Roncella Claudia, Fontanini Gabriella, Sensi Elisa, Falcone Alfredo
Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Via Roma 67, 56100 Pisa, Italy.
Department of Oncology, Ospedale Civile-Istituto Toscano Tumori, Livorno, Italy.
Exp Hematol Oncol. 2017 Mar 21;6:6. doi: 10.1186/s40164-017-0067-4. eCollection 2017.
The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs.
A female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation. After chemotherapy failure, she underwent compassionate treatment with trametinib. Trametinib showed good activity and efficacy, with 48% shrinkage of a metastatic lymphadenopathy after 4 months' treatment. However, the patient reported treatment-related skin toxicity that required dosage reduction and a personalized intermittent trametinib dosing schedule. After over 36 months from the first trametinib administration, and resection of a metastatic lymphadenopathy, the patient experienced complete response.
This case report shows that trametinib could be a valid therapeutic option in patients with metastatic melanoma harboring the rare BRAF K601E mutation.
BRAF K601E突变见于5%的黑色素瘤患者，是BRAF突变的第三常见类型。然而，BRAF和丝裂原活化细胞外信号调节激酶（MEK）抑制剂仅被批准用于BRAF V600阳性黑色素瘤患者，K601E突变的黑色素瘤患者无法使用此类药物。
一名女性患者被诊断为携带BRAF K601E突变的高肿瘤负荷转移性黑色素瘤。化疗失败后，她接受了曲美替尼的同情用药治疗。曲美替尼显示出良好的活性和疗效，治疗4个月后一处转移性淋巴结缩小了48%。然而，患者报告了与治疗相关的皮肤毒性，需要减少剂量并制定个性化的曲美替尼间歇给药方案。自首次使用曲美替尼36个月以上并切除一处转移性淋巴结后，患者实现了完全缓解。
本病例报告表明，曲美替尼可能是携带罕见BRAF K601E突变的转移性黑色素瘤患者的有效治疗选择。
