Mateus Christine, Robert Caroline
Institut Gustave-Roussy, service de dermatologie, 39, rue Camille-Desmoulins, 94805 Villejuif, France.
Bull Cancer. 2012 Jun;99(6):619-25. doi: 10.1684/bdc.2012.1594.
The treatment of metastatic melanoma is presently in complete revolution. Two molecules have recently been authorized for this indication. These treatments have a very different mechanism of action compared to previous chemotherapies. Vemurafenib is a targeted therapy, which blocks BRAF selectively. This molecule induces objective responses in more than 50 % of the patients with V600E mutated melanoma and a benefit in terms of overall survival. However, many patients relapse after about 6 to 8 months of treatment. Many mechanisms are evoked to explain these secondary resistances to therapy. Ipilimumab is an immunotherapy that blocks CTLA4, a physiological brake of lymphocyte activation. With ipilimumab, the objective responses are less frequent than with vemurafenib but are more prolonged over time. Two phases III have demonstrated that ipilimumab treatment is effective on the overall survival of patients with metastatic melanoma. New combination therapies and additional targeted and immunotherapy agents are exciting perspectives that make us more optimistic for the future of metastatic melanoma treatment.
转移性黑色素瘤的治疗目前正处于彻底变革之中。最近有两种分子药物被批准用于该适应症。与以往的化疗相比,这些治疗方法的作用机制截然不同。维莫非尼是一种靶向疗法,可选择性阻断BRAF。该分子可使超过50%的V600E突变型黑色素瘤患者产生客观反应,并在总生存期方面带来益处。然而,许多患者在治疗约6至8个月后复发。人们提出了许多机制来解释这些对治疗的继发性耐药。伊匹单抗是一种免疫疗法,可阻断CTLA4,这是淋巴细胞激活的一种生理制动机制。使用伊匹单抗时,客观反应的频率低于维莫非尼,但随着时间的推移持续时间更长。两项III期试验表明,伊匹单抗治疗对转移性黑色素瘤患者的总生存期有效。新的联合疗法以及更多的靶向和免疫治疗药物是令人振奋的前景,让我们对转移性黑色素瘤治疗的未来更加乐观。