Mo Jeremy, Zaremba Anne, Inderjeeth Andrisha-Jade, El Zeinaty Perla, Li Ao, Wicky Alexandre, Della Marta Nicholas, Marqueste Caroline Gaudy, Bohne Ann-Sophie, Matias Margarida, McNamee Nicholas, Festino Lucia, Chen Charley, Ch'ng Sydney, van Akkooi Alexander C J, Meda Laetitia Da, Park John J, Ascierto Paolo A, Hauschild Axel, Lee Jenny H, Grob Jean Jacques, Mangana Joanna, Guminski Alex, Michielin Olivier, Xu Wen, Lebbe Celeste, Sandhu Shahneen, Zimmer Lisa, Menzies Alexander M, Lo Serigne N, Long Georgina V, Carlino Matteo S, da Silva Ines Pires
Westmead Hospital, Westmead, Australia.
Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Eur J Cancer. 2025 Feb 25;217:115254. doi: 10.1016/j.ejca.2025.115254. Epub 2025 Jan 27.
Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.
This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy.
One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median follow-up of 28.7 months (95 % CI: 21.4-38.3), ORR was 57.3 %, median DOR was 42.8 months (95 % CI, 25.8 - not reached (NR)), median PFS was 14 months (95 % CI, 8.1- 19.8), and median OS was 42.8 months (95 % CI, 30.3 - NR). One-hundred and eight patients (59 %) experienced progressive disease; 50 % (n = 54/108) with primary resistance and 26 % (n = 28/108) with secondary resistance. Fifty patients (27 %; n = 50/185) received subsequent systemic therapies (+/- local therapy) with response data; 18 (36 %; n = 18/50) received doublet platinum chemotherapy (ORR 67 %, DOR 5.0 months [95 % CI; 3.7 - NR]) and 16 (32 %; n = 16/50) were rechallenged with anti-PD-(L)1 (ORR 56 %, DOR 20.2 months [95 % CI; 8.3 - NR]).
The most common subsequent treatment for patients with primary resistance was chemotherapy, while those with secondary resistance most frequently underwent further anti-PD-(L)1 therapy in combination with other therapies. Despite both therapies demonstrating promising ORR, doublet platinum chemotherapy had a poorer DOR compared to anti-PD-(L)1 rechallenge.
默克尔细胞癌（MCC）是一种罕见的皮肤癌，在全球范围内发病率呈上升趋势。抗程序性死亡-1/配体-1（抗PD-(L)1）疗法对晚期MCC的治疗有效。本研究探讨晚期MCC对抗PD-(L)1疗法的反应/进展模式，并描述后续治疗情况。
这是一项多中心国际回顾性队列研究，收集了截至2023年5月来自6个国家17个中心的数据。观察指标包括抗PD-(L)1及后续治疗的客观缓解率（ORR）、缓解持续时间（DOR）、无进展生存期（PFS）和总生存期（OS）。
185例晚期MCC患者接受了抗PD-(L)1治疗。中位随访28.7个月（95%CI：21.4 - 38.3），ORR为57.3%，中位DOR为42.8个月（95%CI，25.8 - 未达到（NR）），中位PFS为14个月（95%CI，8.1 - 19.8），中位OS为42.8个月（95%CI，30.3 - NR）。108例患者（59%）出现疾病进展；50%（n = 54/108）为原发性耐药，26%（n = 28/108）为继发性耐药。50例患者（27%；n = 50/185）接受了后续全身治疗（±局部治疗）并获得反应数据；18例（36%；n = 18/50）接受了双联铂类化疗（ORR为67%，DOR为5.0个月[95%CI；3.7 - NR]），16例（32%；n = 16/50）再次接受抗PD-(L)1治疗（ORR为56%，DOR为20.2个月[95%CI；8.3 - NR]）。
原发性耐药患者最常见的后续治疗是化疗，而继发性耐药患者最常接受进一步的抗PD-(L)1治疗联合其他治疗。尽管两种治疗的ORR都很有前景，但双联铂类化疗的DOR比再次接受抗PD-(L)1治疗要差。
