Real-world outcomes of pembrolizumab in advanced anal cancer: a nationwide Danish anal Cancer Group report
DOI:
https://doi.org/10.2340/1651-226X.2026.44690Keywords:
Anal cancer, Squamous cell carcinoma, Immune checkpoint inhibitors, Antibodies monoclonal humanisedAbstract
Background and purpose: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy with limited treatment options for advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have shown durable responses in clinical trials, but evidence derives from small and highly selected populations. This study investigates the effectiveness and tolerability of pembrolizumab in an unselected real-world cohort.
Patient/material and methods: This retrospective, multicenter cohort study evaluated the real-world efficacy, durability, and safety of pembrolizumab in Danish patients with advanced or metastatic SCCA treated between September 2018 and September 2023. A total of 37 patients, who received at least one dose of pembrolizumab for non-resectable, recurrent or metastatic disease, were included (89% ≥ 2nd line). Median age was 64 years, the majority were female (64.9%), and most tumours were human papillomavirus (HPV) (p16) positive (73.0%).
Results: The objective response rate (ORR) was 13.5%, with two complete and three partial responses. The clinical benefit rate (CBR) was 48.6%, and two patients had durable responses exceeding 24 months. Median progression-free survival (PFS) and overall survival (OS) were 4.0 months 95% confidence interval (CI) (2.6–5.5) and 12.1 months 95% CI (7.6–15.2), respectively. Patients with good performance status and HPV-positive disease had significantly improved survival outcomes. Treatment was well tolerated, and no treatment-related deaths were reported.
Interpretation: In this real-world cohort, pembrolizumab demonstrated durable responses in a subset of patients with advanced SCCA and an acceptable safety profile. Outcomes were comparable to clinical trial data, indicating modest activity. Findings support using pembrolizumab as a treatment option in selected patients, but further evidence is needed to refine its role.
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Islami F, Ferlay J, Lortet-Tieulent J, Bray F, Jemal A. International trends in anal cancer incidence rates. Int J Epidemiol. 2017;46(3):924–38. DOI: https://doi.org/10.1093/ije/dyx200
Johnsson A, Norman D, Angenete E, Cavalli-Björkman N, Lagerbäck C, Leon O, et al. Anal cancer in Sweden 2015–2019. Implementation of guidelines, structural changes, national registry and early results. Acta Oncol. 2022;61(5):575–82. DOI: https://doi.org/10.1080/0284186X.2022.2048069
Rao S, Guren MG, Khan K, Brown G, Renehan AG, Steigen SE, et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021;32(9):1087–100. DOI: https://doi.org/10.1016/j.annonc.2021.06.015
Rao S, Sclafani F, Eng C, Adams RA, Guren MG, Sebag-Montefiore D, et al. International rare cancers initiative multicenter randomized phase ii trial of cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer: InterAAct. J Clin Oncol. 2020;38(22):2510–8. DOI: https://doi.org/10.1200/JCO.19.03266
Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990;63(6):1129–36. DOI: https://doi.org/10.1016/0092-8674(90)90409-8
Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248(4951):76–9. DOI: https://doi.org/10.1126/science.2157286
Sclafani F, Rao S. Systemic therapies for advanced squamous cell anal cancer. Curr Oncol Rep. 2018;20(7):53. DOI: https://doi.org/10.1007/s11912-018-0698-6
Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28(5):1036–41. DOI: https://doi.org/10.1093/annonc/mdx029
Marabelle A, Cassier PA, Fakih M, Kao S, Nielsen D, Italiano A, et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Lancet Gastroenterol Hepatol. 2022;7(5):446–54. DOI: https://doi.org/10.1016/S2468-1253(21)00382-4
Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(4):446–53. DOI: https://doi.org/10.1016/S1470-2045(17)30104-3
Rao S, Anandappa G, Capdevila J, Dahan L, Evesque L, Kim S, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. 2022;7(4):100529. DOI: https://doi.org/10.1016/j.esmoop.2022.100529
Rao S, Samalin-Scalzi E, Evesque L, Ben Abdelghani M, Morano F, Roy A, et al. POD1UM-303/InterAACT-2 study investigators. Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial. Lancet. 2025;405(10495):2144–52. DOI: https://doi.org/10.1016/S0140-6736(25)00631-2
Dhawan N, Afzal MZ, Amin M. Immunotherapy in anal cancer. Curr Oncol. 2023;30(5):4538–50. DOI: https://doi.org/10.3390/curroncol30050343
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. DOI: https://doi.org/10.1016/S0140-6736(07)61602-X
Huffman BM, Singh H, Ali LR, Horick N, Wang SJ, Hoffman MT, et al. Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders. J Immunother Cancer. 2024;12(1):e008436. DOI: https://doi.org/10.1136/jitc-2023-008436
Kim S, Ghiringhelli F, de la Fouchardière C, Evesque L, Smith D, Badet N, et al. Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study. Lancet Oncol. 2024;25(4):518–28. DOI: https://doi.org/10.1016/S1470-2045(24)00081-0
Lonardi S, Prete AA, Morano F, Messina M, Formica V, Corsi DC, et al. Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study. J Immunother Cancer. 2021;9(11):e002996. DOI: https://doi.org/10.1136/jitc-2021-002996
Morris VK, Liu S, Lin K, Zhu H, Prasad S, Mahvash A et al. Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal. Clin Cancer Res. 2025;31(9):1657–66. DOI: https://doi.org/10.1158/1078-0432.CCR-24-1512
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Copyright (c) 2026 Karen-Lise Garm Spindler, Christian Andreas Hvid, Lars Ulrik Fokdal, Karen Lycke Wind, Anne Vittrup Jakobsen, Rikke Løvendahl Eefsen, Eva Serup-Hansen
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