Perioperative Pembrolizumab in Locally Advanced Melanoma: A Real-world Single-centre Retrospective Study

Authors

DOI:

https://doi.org/10.2340/actadv.v106.adv-2025-0009

Keywords:

melanoma, neoadjuvant therapy, immunotherapy, pembrolizumab, retrospective studies, surgery

Abstract

Perioperative immune-checkpoint inhibition (ICI) using pembrolizumab (3 doses of pembrolizumab 200 mg every 3 weeks before surgery and 15 doses afterwards) in advanced resectable melanoma has shown substantial pathological response rates and improved event-free survival (EFS) compared to postoperative (adjuvant) ICI. Real-world evidence on efficacy and safety of perioperative ICI in melanoma remains limited. In this retrospective single-centre study, 20 patients with resectable stage IIIB–IV melanoma were treated with perioperative pembrolizumab. Radiological and pathological responses, early survival outcomes and treatment-related adverse events were analysed at a median follow-up of 13.9 months. Eighteen patients (18/20) underwent surgery. A pathological complete response was observed in 44% (8/18), while 56% (10/18) showed a pathological non-response. No patient (0/18) had a pathological partial response. One-year EFS was 66.5% (95% confidence interval (CI) 47.3–93.3), 1-year relapse-free survival 77.6% (95% CI 57.9–100) and 1-year overall survival 89.2% (95% CI 76.0–100, identical with 1-year melanoma-specific survival). Immune-related adverse events occurred in 50% of the patients (≥grade 3 in 15%). Our study confirms the feasibility of perioperative pembrolizumab in a real-world setting and shows promising efficacy and tolerability in melanoma. Pathological response may guide surgical and adjuvant strategies.

Downloads

Download data is not yet available.

References

Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, et al. Final 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2025; 392: 11–22. DOI: https://doi.org/10.1056/NEJMoa2407417

Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371: 1867–1876. DOI: https://doi.org/10.1056/NEJMoa1408868

Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378: 1789–1801. DOI: https://doi.org/10.1056/NEJMoa1802357

Boulva K, Apte S, Yu A, Tran A, Shorr R, Song X, et al. Contemporary neoadjuvant therapies for high-risk melanoma: A systematic review. Cancers (Basel) 2021; 13: 1905. DOI: https://doi.org/10.3390/cancers13081905

Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science (New York, NY) 2020; 367: eaax0182. DOI: https://doi.org/10.1126/science.aax0182

Rozeman EA, Menzies AM, van Akkooi ACJ, Adhikari C, Bierman C, van de Wiel BA, et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): A multicentre, phase 2, randomised, controlled trial. Lancet Oncol 2019; 20: 948–960. DOI: https://doi.org/10.1016/S1470-2045(19)30151-2

Reijers ILM, Menzies AM, van Akkooi ACJ, Versluis JM, van den Heuvel NMJ, Saw RPM, et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: The PRADO trial. Nat Med 2022; 28: 1178–1188. DOI: https://doi.org/10.1038/s41591-022-01851-x

Patel SP, Othus M, Chen Y, Wright GP, Jr, Yost KJ, Hyngstrom JR, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med 2023; 388: 813–823. DOI: https://doi.org/10.1056/NEJMoa2211437

Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda M, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Engl J Med 2024; 391: 1696–1708. DOI: https://doi.org/10.1056/NEJMoa2402604

Schummer P, Glutsch V, Haug L, Rosenfeldt M, Lock J, Meir M, et al. Neoadjuvant ipilimumab plus nivolumab in locally advanced melanoma: A real-world single-centre retrospective study. EJC Skin Cancer 2023; 1: 100003. DOI: https://doi.org/10.1016/j.ejcskn.2023.100003

Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67: 472–492. DOI: https://doi.org/10.3322/caac.21409

Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer 2016; 62: 132–137. DOI: https://doi.org/10.1016/j.ejca.2016.03.081

Amaria RN, Menzies AM, Burton EM, Scolyer RA, Tetzlaff MT, Antdbacka R, et al. Neoadjuvant systemic therapy in melanoma: Recommendations of the International Neoadjuvant Melanoma Consortium. Lancet Oncol 2019; 20: e378–e389.

Patel S, Othus M, Wright P, Hyngstrom J, Lao CD, Truong TG, et al. LBA48 Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIb-IV melanoma from SWOG S1801. Ann Oncol 2023; 34: S1288. DOI: https://doi.org/10.1016/j.annonc.2023.10.042

Nardin C, Cavalieri C, Lebbé C, Gérard E, Puyraveau M, Vergara R, et al. Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL). Br J Dermatol 2025 Jul 14. [Online ahead of print] DOI: https://doi.org/10.1093/bjd/ljaf268

Nardin C, Cavalieri C, Lebbe C, Pagès C, Gérard E, Rouanet J, et al. Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL). JCO 2024; 42: 9578–9578. DOI: https://doi.org/10.1200/JCO.2024.42.16_suppl.9578

Nelson A, Krabbe E, Björkström K, Huibers A, Jovanovic B, Blank CU, et al. Neoadjuvant immunotherapy for patients with resectable stage III/IV cutaneous melanoma - A Swedish retrospective real-world study (NEO-MEL). Eur J Cancer 2025; 224: 115485. DOI: https://doi.org/10.1016/j.ejca.2025.115485

Tomsitz D, Zimmermann P, Kunz WG, Neumann J, Siegmund BJ, Weiss BG, et al. Neoadjuvant treatment with immune checkpoint inhibitors in patients with melanoma: A real-life retrospective study. J Dtsch Dermatol Ges 2025; 23: 600–608. DOI: https://doi.org/10.1111/ddg.15632

Iacono D, Vitale MG, Basile D, Pelizzari G, Cinausero M, Poletto E, et al. Immunotherapy for older patients with melanoma: From darkness to light? Pigment Cell Melanoma Res 2021; 34: 550–563. DOI: https://doi.org/10.1111/pcmr.12917

Lodde GC, Hassel JC, von Wasielewski I, Meier F, Mohr P, Köhler K, et al. Long-term follow-up of real-world adjuvant anti-PD1 checkpoint inhibition and targeted therapy in stage III melanoma patients. J Clin Oncol 2025 DOI: https://doi.org/10.1200/JCO-24-02776

Cabrita R, Lauss M, Sanna A, Donia M, Skaarup Larsen M, Mitra S, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature New Biol 2020; 577: 561–565. DOI: https://doi.org/10.1038/s41586-019-1914-8

Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda MI, et al. Neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in macroscopic, resectable stage III melanoma: The phase 3 NADINA trial. JCO 2024; 42: LBA2–LBA2. DOI: https://doi.org/10.1200/JCO.2024.42.17_suppl.LBA2

Published

2026-01-19

How to Cite

Goller, S., Dege, T., Schummer, P., Haug, L., Meir, M., Gehrke, T., … Glutsch, V. (2026). Perioperative Pembrolizumab in Locally Advanced Melanoma: A Real-world Single-centre Retrospective Study. Acta Dermato-Venereologica, 106, adv–2025. https://doi.org/10.2340/actadv.v106.adv-2025-0009

Issue

Section

Articles