Kaehler Katharina C, Blome Christine, Forschner Andrea, Gutzmer Ralf, Haalck Thomas, Heinzerling Lucie, Kornek Thomas, Livingstone Elisabeth, Loquai Carmen, Maul Lara Valeska, Lang Berenice M, Schadendorf Dirk, Stade Barbara, Terheyden Patrick, Utikal Jochen, Wagner Tobias, Hauschild Axel, Garbe Claus, Augustin Matthias
Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg, Hamburg Department of Dermatology, Eberhard-Karls University of Tuebingen, Tuebingen Skin Cancer Center Hannover, Hannover University of Hamburg, Hamburg Department of Dermatology, University Hospital Erlangen, Erlangen TABEA Clinic, Hamburg Department of Dermatology, University Hospital Essen, Essen Department of Dermatology, University of Mainz, Mainz MSD Sharp & Dohme GmbH, Munich Department of Dermatology, University Hospital (UKSH), Campus Lübeck, Luebeck Skin Cancer Unit, German Cancer Research Center (DKFZ) Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany.
Medicine (Baltimore). 2016 Nov;95(46):e5375. doi: 10.1097/MD.0000000000005375.
Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.
目前,干扰素α-2b(IFNα-2b)是一种已获批用于高危黑色素瘤患者的辅助药物,可改善无病生存期(DFS)。然而,尚不清楚它是否也会影响总生存期。辅助性高剂量IFNα的广泛应用因其显著的毒性和有限的疗效而受到限制。当前的治疗策略,如免疫检查点阻断或靶向治疗,在辅助治疗中可能也有用。因此,权衡可能的副作用和治疗益处之间的利弊很重要。我们评估了患者对与IFN治疗相关健康状态的效用值。效用值是指在从0(死亡)到1(完美健康)的量表上对特定健康状态的偏好衡量指标。使用标准博弈技术,在130名德国低危黑色素瘤患者中确定了与辅助性IFN相关的健康状态的效用值。评估了四种IFNα-2b毒性情况以及以下三种治疗后结果:无病健康状态和黑色素瘤复发(无论之前是否使用过IFNα-2b)导致癌症死亡。要求患者在5年DFS的改善和IFN相关副作用之间进行权衡。黑色素瘤复发的效用值(平均0.60)显著低于所有IFNα-2b毒性情况的效用值(平均0.81 - 0.90)。患者分别愿意为5年DFS有50%和75%的机会而耐受轻度至中度和重度毒性。效用值和阈值益处大多与患者特征如性别、收入和社会状况无关。仅年龄和既往个人癌症经历有显著影响。平均而言,德国患者愿意用甚至严重的IFNα-2b毒性来换取降低黑色素瘤复发率。这一结果指出了无复发生存期对黑色素瘤患者的重要性。我们研究中测量的效用值可应用于新辅助药物临床试验的决策过程。