van Not Olivier J, de Meza Melissa M, van den Eertwegh Alfons J M, Haanen John B, Blank Christian U, Aarts Maureen J B, van den Berkmortel Franchette W P J, van Breeschoten Jesper, de Groot Jan-Willem B, Hospers Geke A P, Ismail Rawa K, Kapiteijn Ellen, Piersma Djura, van Rijn Roos S, Stevense-den Boer Marion A M, van der Veldt Astrid A M, Vreugdenhil Gerard, Bonenkamp Han J, Boers-Sonderen Marye J, Blokx Willeke A M, Wouters Michel W J M, Suijkerbuijk Karijn P M
Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584CX, the Netherlands.
Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333ZC, the Netherlands.
Eur J Cancer. 2022 May;167:70-80. doi: 10.1016/j.ejca.2022.02.026. Epub 2022 Apr 5.
Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM).
We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS.
In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8-5.6) than patients with CM (10.1 months; 95%CI: 8.5-12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26-2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15-2.06; P = 0.004) than CM.
This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.
近期报告显示免疫检查点抑制剂在晚期肢端黑色素瘤（AM）中的疗效有限。本研究旨在调查免疫检查点抑制剂在Ⅲ期和Ⅳ期AM患者中的临床结局，并与皮肤黑色素瘤（CM）患者进行比较。
我们纳入了在前瞻性全国性荷兰黑色素瘤治疗登记处登记的接受一线抗程序性细胞死亡（PD）-1单药治疗或伊匹木单抗-纳武单抗治疗的晚期AM和CM患者。计算客观缓解率、无进展生存期（PFS）和总生存期（OS）。使用Cox比例风险模型评估PFS和OS的预后因素。
总共纳入了2058例晚期黑色素瘤患者（88例AM和1970例CM）。在晚期抗PD-1队列中，AM的一线客观缓解率为34%，而CM为54%；在晚期伊匹木单抗-纳武单抗队列中，AM为33%，CM为53%。抗PD-1治疗的AM患者的中位PFS（3.1个月；95%CI：2.8-5.6）明显短于CM患者（10.1个月；95%CI：8.5-12.2）（P<0.001）。在晚期黑色素瘤患者中，AM与CM相比，进展风险（HRadj 1.63；95%CI：1.26-2.11；P<0.001）和死亡风险（HRadj 1.54；95%CI：1.15-2.06；P=0.004）显著更高。
本研究表明抗PD-1单药治疗和伊匹木单抗-纳武单抗在AM中的有效性较低，其缓解率、PFS和OS均低于CM。在替代治疗策略的开发中，应优先考虑这组患者。
