Bottlaender L, Amini-Adle M, Maucort-Boulch D, Robinson P, Thomas L, Dalle S
Department of Dermatology, ImmuCare, Cancer Research Centre of Lyon, Centre Hospitalier Lyon Sud, Lyon 1 University, Pierre Bénite Cedex, France.
Service de Biostatistique - Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Lyon, France.
J Eur Acad Dermatol Venereol. 2020 Sep;34(9):2096-2105. doi: 10.1111/jdv.16311. Epub 2020 Apr 27.
Cutaneous adverse events (AEs) are the most prevalent toxicity under checkpoint inhibitors in clinical trials. In 'real-life' conditions of use, skin toxicities under anti-PD-1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti-PD-1 therapy under 'real-life' conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyse associated extra-cutaneous toxicities, progression-free survival (PFS) and overall survival (OS).
Advanced melanoma patients treated with nivolumab or pembrolizumab between August 2014 and October 2017 were included. Patients lost to follow-up or receiving anti-PD-1 as part of a clinical trial were excluded.
One hundred and eighty-nine patients with metastatic melanoma (with 109 men (57.7%) were included. Cutaneous AE occurred in 39 patients (20.6%). The three most prevalent cutaneous AEs were skin eruption (macular-papular or eczematous) (n = 18, 9.5%), vitiligo (n = 16; 8.5%) and isolated pruritus (n = 5, 2.6%). Grade 3-4 skin toxicity was diagnosed in five patients (2.6%). Atopy (28.2% vs. 12.0%; P = 0.024), hypereosinophilia (20.5% vs. 8.7%; P = 0.046), thyroiditis (17.9% vs. 4.7%; P = 0.011) and renal toxicity (15.4% vs. 4%; P = 0.019) were significantly associated with cutaneous AE. Patients with skin eruption (log-rank = 0.001), vitiligo (log-rank = 0.001) and any type of cutaneous AE (log-rank < 0.001) had a better overall survival.
Cutaneous AEs are frequent and often manageable toxicity and were a predictor of tumour response in melanoma patients under anti-PD-1 therapy in this cohort.
皮肤不良事件（AE）是临床试验中检查点抑制剂治疗下最常见的毒性反应。在“实际使用”情况下，抗PD - 1治疗下的皮肤毒性迄今尚未在大型队列中得到描述。本研究的目的是确定在“实际使用”情况下接受抗PD - 1治疗的晚期黑色素瘤患者皮肤毒性的临床特征。次要目标是评估出现皮肤毒性的患者特征，并分析相关的皮肤外毒性、无进展生存期（PFS）和总生存期（OS）。
纳入2014年8月至2017年10月期间接受纳武单抗或派姆单抗治疗的晚期黑色素瘤患者。排除失访患者或作为临床试验一部分接受抗PD - 1治疗的患者。
纳入189例转移性黑色素瘤患者（其中男性109例（57.7%））。39例患者（20.6%）发生皮肤AE。三种最常见的皮肤AE为皮疹（斑丘疹或湿疹样）（n = 18，9.5%）、白癜风（n = 16；8.5%）和单纯瘙痒（n = 5，2.6%）。5例患者（2.6%）被诊断为3 - 4级皮肤毒性。特应性（28.2%对12.0%；P = 0.024）、嗜酸性粒细胞增多（20.5%对8.7%；P = 0.046）、甲状腺炎（17.9%对4.7%；P = 0.011）和肾毒性（15.4%对4%；P = 0.019）与皮肤AE显著相关。出现皮疹（对数秩检验=0.001）、白癜风（对数秩检验=0.001）和任何类型皮肤AE（对数秩检验<0.001）的患者总生存期较好。
皮肤AE是常见且通常可控制的毒性反应，并且是该队列中接受抗PD - 1治疗的黑色素瘤患者肿瘤反应的预测指标。
