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Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma

Grover, P.
; 
Lo, S. N.
; 
Li, I.
; 
Kuijpers, A. M. J.
; 
Kreidieh, F.
; 
Williamson, A.
; 
Amaral, T.
; 
Dimitriou, F.
; 
Placzke, J.
; 
Olino, K.
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Abstract
BACKGROUND: Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear. PATIENTS AND METHODS: In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined. RESULTS: A total of 628 patients from 34 centres across Australia, Europe and the United States were identified-256 in anti-PD-1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (interquartile range 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD-1 compared with OBS. The 2-year RFS was 79.3% [95% confidence interval (CI) 74.1% to 84.8%] for anti-PD-1, 98.6% (95% CI 96.0% to 100%) for TT and 84.3% (95% CI 79.9% to 89.0%) for OBS. The 2-year DMFS was 88.4% (95% CI 84.3% to 92.8%) in anti-PD-1, 100% in TT and 91.1% (95% CI 87.7% to 94.7%) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in anti-PD-1 and OBS (P < 0.05). Rates of ≥grade 3 toxicities were 10.9% with anti-PD-1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in the anti-PD-1 group and 12.5% in the TT group. CONCLUSIONS: Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD-1 did not significantly improve RFS or DMFS compared with OBS alone. Adjuvant TT appears promising over anti-PD-1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow-up or prospective randomised trials.
Authors
Grover, P.
Lo, S. N.
Li, I.
Kuijpers, A. M. J.
Kreidieh, F.
Williamson, A.
Amaral, T.
Dimitriou, F.
Placzke, J.
Olino, K.
Vitale, M. G.
Saiag, P.
Gutzmer, R.
Allayous, C.
Olofsson Bagge, R.
Mattsson, J.
Asher, N.
Carter, T. J.
Meniawy, T. M.
Lawless, A. R.
Czapla, J. A.
Warburton, L.
Gaudy-Marqueste, C.
Grob, J. J.
Collins, R. G.
Zhang, E.
Kessels, J. I.
Neyns, B.
Mehmi, I.
Hamid, O.
Julve, M.
Furness, A. J. S.
Margolin, K. A.
Lev-Ari, S.
Ressler, J. M.
Haque, W.
Khattak, M. A.
Wicky, A.
Roberts-Thomson, R.
Arance, A.
Warrier, G.
Schollenberger, M. D.
Parente, P.
Chatziioannou, E.
Lipson, E. J.
Michielin, O.
Weber, J. S.
Hoeller, C.
Larkin, J.
Atkins, M. B.
Essner, R.
Johnson, D. B.
Sullivan, R. J.
Nathan, P.
Schachter, J.
Lebbe, C.
Ascierto, P. A.
Kluger, H.
Rutkowski, P.
Dummer, R.
Garbe, C.
Lorigan, P. C.
Burton, E.
Tawbi, H. A.
Haanen, J.
Carlino, M. S.
Menzies, A. M.
Long, G. V.
Affiliation
Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia. Melanoma Institute Australia, The University of Sydney, Sydney, Australia. Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. The Christie NHS Foundation Trust, Manchester, UK. Center for Dermato-oncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. Department of Dermatology, Faculty of Medicine, University Hospital of Zurich, Zurich, Switzerland. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. Yale University School of Medicine, Smilow Cancer Center, New Haven Hospital, New Haven, USA. Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione 'G. Pascale', Naples, Italy. University Department of Dermatology, Université de Versailles-Saint Quentin en Yvelines, APHP, Boulogne, France. Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany. AP-HP Dermato-oncology, Cancer Institute APHP Nord Paris Cité, Saint Louis Hospital, Paris, France. Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg. Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel HaShomer, Israel. Mount Vernon Cancer Centre, Northwood, UK. Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Perth, Australia. Aix-Marseille Univ, APHM, Hôpital Timone, Service de dermatologie et de cancérologie cutanée, Marseille, France. Vanderbilt University School of Medicine, Nashville, USA. Department of Surgery, Westmead Hospital, Sydney, Australia. Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium. Cedars-Sinai The Angeles Clinic and Research Institute, Los Angeles, USA. Renal, Skin and Cell Therapy Unit, The Royal Marsden NHS Foundation Trust, London, UK. Department of Medical Oncology, Providence St. John's Cancer Institute, Santa Monica. Georgetown Lombardi Comprehensive Cancer Center, Washington, USA. Department of Dermatology, Medical University of Vienna, Vienna, Austria. Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, USA. Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia. Oncology, Lausanne University Hospital, Lausanne, Switzerland. Medical Oncology Department, The Queen Elizabeth Hospital, Adelaide, Australia. Hospital Clínic Barcelona and IDIBAPS, Barcelona, Spain. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins, Baltimore, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University SOM, Baltimore, USA. Eastern Health Clinical School, Box Hill Hospital, Monash University, Melbourne, Australia. Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Department of Surgery, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, USA. Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, USA. Sheba Medical Center-Tel HaShomer, Ramat Gan, Israel. Université Paris Cite, APHP Dermato-oncology, Cancer Institute APHP Nord Paris Cité, INSERM U976, Saint Louis Hospital, Paris, France. The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Westmead and Blacktown Hospitals, University of Sydney, Melanoma Institute Australia, Sydney, Australia. Melanoma Institute Australia, University of Sydney, Mater and Royal North Shore Hospitals, Australia. Melanoma Institute Australia, University of Sydney, Mater and Royal North Shore Hospitals, Australia. Electronic address: Georgina.long@sydney.edu.au.
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Date
2025
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All Christie Publications
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Article
Citation
Grover P, Lo SN, Li I, Kuijpers AMJ, Kreidieh F, Williamson A, et al. Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma. Annals of oncology : official journal of the European Society for Medical Oncology. 2025 Jul;36(7):807-18. PubMed PMID: 40204154. Epub 2025/04/10. eng.
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https://christie.openrepository.com/handle/10541/627690
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