Ugurel Selma, Röhmel Joachim, Ascierto Paolo A, Flaherty Keith T, Grob Jean Jacques, Hauschild Axel, Larkin James, Long Georgina V, Lorigan Paul, McArthur Grant A, Ribas Antoni, Robert Caroline, Schadendorf Dirk, Garbe Claus
Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
28355 Bremen, Germany.
Eur J Cancer. 2016 Jan;53:125-34. doi: 10.1016/j.ejca.2015.09.013. Epub 2015 Dec 17.
The survival of advanced metastatic melanoma has been greatly improved within the past few years. New therapeutic strategies like kinase inhibitors for BRAF-mutant melanoma and immune checkpoint blockers proved to prolong survival times within clinical trials, and many of them have already entered routine clinical use. However, these different treatment modalities have not yet been tested against each other, which complicate therapy decisions. We performed an explorative analysis of survival data from recent clinical trials. Thirty-five Kaplan-Meier survival curves from 17 trials were digitised, re-grouped by matching inclusion criteria and treatment line, and averaged by therapy strategy. Notably, the survival curves grouped by therapy strategy revealed a very high concordance, even if different agents were used. The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes. For first-line therapy, averaged survival proportions of patients alive at 12 months were 74.5% with BRAF plus MEK inhibitor treatment versus 71.9% with PD-1 blockade. This explorative comparison shows the kinase inhibitors as similarly effective as immune checkpoint blockers with regard to survival. However, to confirm these first trends for implementation into an individualised treatment of melanoma patients, data from prospective clinical trials comparing the different treatment strategies head-to-head have to be awaited.
在过去几年中,晚期转移性黑色素瘤患者的生存率有了显著提高。新的治疗策略,如针对BRAF突变型黑色素瘤的激酶抑制剂和免疫检查点阻断剂,在临床试验中被证明可延长生存期,其中许多已进入常规临床应用。然而,这些不同的治疗方式尚未相互比较,这使得治疗决策变得复杂。我们对近期临床试验的生存数据进行了探索性分析。将17项试验中的35条Kaplan-Meier生存曲线数字化,根据纳入标准和治疗线进行匹配重新分组,并按治疗策略进行平均。值得注意的是,即使使用了不同的药物,按治疗策略分组的生存曲线显示出非常高的一致性。分别使用BRAF加MEK抑制剂以及程序性死亡1(PD1)阻断剂联合或不联合细胞毒性T淋巴细胞相关抗原4(CTLA-4)阻断剂时,观察到最大的生存改善,这两种治疗策略显示出相似的生存结果。对于一线治疗,BRAF加MEK抑制剂治疗组12个月时存活患者的平均生存比例为74.5%,而PD-1阻断治疗组为71.9%。这项探索性比较表明,在生存方面,激酶抑制剂与免疫检查点阻断剂同样有效。然而,要确认这些初步趋势以用于黑色素瘤患者的个体化治疗,还需等待比较不同治疗策略的前瞻性临床试验数据。