Plastic and Reconstructive Surgery, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Arch Dermatol Res. 2012 Apr;304(3):177-84. doi: 10.1007/s00403-012-1223-7. Epub 2012 Feb 17.
Prognosis for advanced and metastatic melanoma is poor, with a 5-year survival of 78, 59 and 40% for patients with stage IIIA, IIIB and IIIC, respectively, and a 1-year survival of 62% for M1a, 53% for M1b and 33% for M1c. The unsatisfactory results of actual standard therapies for metastatic melanoma highlight the need for effective new therapeutic strategies. Several drugs, including BRAF, KIT and MEK inhibitors, are currently being evaluated after promising data from Phase I and Phase II studies; Vemurafenib, a BRAF-inhibitor agent, has been approved by the Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation after a significant impact on both progression-free and overall survival was demonstrated compared with dacarbazine in a Phase III trial. Ipilimumab, an immunotherapeutic drug, has proven to be capable of inducing long-lasting responses and was approved for patients with advanced melanoma in first- and second-line treatment by the FDA and in second-line treatment by the European Medicines Agency. Furthermore, a significant survival benefit of the combination of ipilimumab with dacarbazine compared with dacarbazine alone for first-line treatment was reported. In the near future, patients with BRAF mutations could have the chance to benefit from treatment with BRAF inhibitors; patients harboring BRAF or NRAS mutations could be treated with MEK inhibitors; finally, the subgroup of patients with acral, mucosal or chronic sun-damaged melanoma harboring a KIT mutation could benefit from KIT inhibitors. Ipilimumab could become a standard treatment for metastatic melanoma, both as a single agent and in combination; its efficacy has been proven, and researchers should now address their efforts to understanding the predictive variables of response to treatment.
晚期和转移性黑色素瘤的预后较差，分别有 78%、59%和 40%的 IIIA、IIIB 和 IIIC 期患者 5 年生存率，M1a、M1b 和 M1c 期患者 1 年生存率分别为 62%、53%和 33%。实际标准疗法治疗转移性黑色素瘤的结果并不理想，这突显了需要新的有效治疗策略。几种药物，包括 BRAF、KIT 和 MEK 抑制剂，在 I 期和 II 期研究取得有希望的数据后正在进行评估；Vemurafenib，一种 BRAF 抑制剂，在 III 期临床试验中与达卡巴嗪相比，对无进展生存期和总生存期均有显著影响后，已被美国食品药品监督管理局（FDA）批准用于治疗 BRAF V600E 突变的不可切除或转移性黑色素瘤患者。Ipilimumab，一种免疫治疗药物，已被证明能够诱导持久的反应，并已被 FDA 批准用于晚期黑色素瘤的一线和二线治疗，被欧洲药品管理局批准用于二线治疗。此外，与单独使用达卡巴嗪相比，ipilimumab 联合达卡巴嗪治疗一线治疗的患者有显著的生存获益。在不久的将来，BRAF 突变的患者有可能受益于 BRAF 抑制剂的治疗；携带 BRAF 或 NRAS 突变的患者可以用 MEK 抑制剂治疗；最后，携带 KIT 突变的肢端、黏膜或慢性日光损伤黑色素瘤亚组的患者可以从 KIT 抑制剂中获益。Ipilimumab 可能成为转移性黑色素瘤的标准治疗方法，无论是单独使用还是联合使用；其疗效已得到证实，研究人员现在应该努力了解对治疗反应的预测变量。
