PD-1 vs PD-L1 Therapy in Advanced Merkel Cell Carcinoma

Comparative Immune Therapy Study  

This international retrospective study compares the effectiveness of anti–PD-1 therapies (pembrolizumab, nivolumab, retifanlimab) versus anti–PD-L1 therapy (avelumab) in patients with advanced Merkel cell carcinoma (MCC).

Background

Immune checkpoint inhibitors (ICIs) have transformed treatment for MCC, leading to a more than two-fold improvement in survival for patients with advanced MCC [1]. Moreover, real-world data confirmed the results of these promising clinical trials on a population level [2]. While both PD-1 and PD-L1 ICIs have demonstrated durable responses, data directly comparing their relative efficacy in MCC is unknown. A recent meta-analysis of 19 randomized clinical trials involving over 11,000 patients and 75 tumor types found PD-1 therapy to exhibit greater overall survival compared to PD-L1 therapy [3]. However, this study did not include MCC specific data. Treatment patterns can also vary geographically, with PD-1 immunotherapy more commonly used in the USA and PD-L1 therapy used more in Europe and Australia.

Proposal

We aim to identify the effectiveness of 1st line anti-PD-1 therapies versus anti-PD-L1 therapies based on world-wide MCC patient data. MC3 will coordinate this multi-site study, led by Jürgen C. Becker, Georg Lodde, and Mazdak Dalkoohi of the German Cancer Consortium (DKTK) and Universitätsmedizin Essen, Germany.

Participating centers will contribute anonymized clinical data for MCC patients who have undergone 1st line PD-1 or PD-L1 immunotherapy.

If you would like to join us as a participating center, please contact us at mc3institute@uw.edu

1. Paulson KG, Park SY, Bhatia S, Hippe DS, Nghiem P. Improved survival at the population level for patients with advanced Merkel cell carcinoma following availability of immunotherapy. J Am Acad Dermatol. 2025;93(1):89-94. doi:10.1016/j.jaad.2025.03.006 
2. Shafique N, Dheer A, Tortorello G, et al. Outcomes of Merkel cell carcinoma in the era of immune checkpoint blockade. Ann Surg Oncol. 2024;31:5502-5503. doi:10.1245/s10434-024-15558-5
3. Duan J, Cui L, Zhao X, et al. Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2020;6(3):375-384. doi:10.1001/jamaoncol.2019.5367