Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017

被引:217
作者
Ugurel, Selma [1 ]
Roehmel, Joachim
Ascierto, Paolo A. [2 ]
Flaherty, Keith T. [3 ]
Grob, Jean Jacques [4 ,5 ]
Hauschild, Axel [6 ]
Larkin, James [7 ]
Long, Georgina V. [8 ,9 ]
Lorigan, Paul [10 ]
McArthur, Grant A. [11 ,12 ]
Ribas, Antoni [13 ]
Robert, Caroline [14 ]
Schadendorf, Dirk [1 ]
Garbe, Claus [15 ]
机构
[1] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Essen, Germany
[2] Ist Nazl Tumori Fdn G Pascale, Melanoma Immunotherapy & Innovat Therapy Unit, Naples, Italy
[3] Massachusetts Gen Hosp, Boston, MA 02114 USA
[4] Timone Hosp, Dept Dermatol, Marseille, France
[5] Aix Marseille Univ, Marseille, France
[6] Univ Hosp Schleswig Holstein, Dept Dermatol, Kiel, Germany
[7] Royal Marsden Hosp NHS Fdn Trust, London, England
[8] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia
[9] Royal North Shore Hosp, Sydney, NSW, Australia
[10] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England
[11] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia
[12] Univ Melbourne, Parkville, Vic, Australia
[13] Univ Calif Los Angeles, Los Angeles, CA USA
[14] Gustave Roussy Canc Campus, Villejuif Grand Paris, France
[15] Univ Tubingen, Dept Dermatol, Ctr Dermatooncol, Tubingen, Germany
关键词
Melanoma; Therapy; Kinase inhibitors; Immune checkpoint blockers; Survival; IPILIMUMAB PLUS DACARBAZINE; OPEN-LABEL; COMBINED NIVOLUMAB; MEK INHIBITION; DOUBLE-BLIND; BRAF; PHASE-3; MULTICENTER; VEMURAFENIB; DABRAFENIB;
D O I
10.1016/j.ejca.2017.06.028
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan-Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:247 / 257
页数:11
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