Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma
Author Identifier
L. Warburton: https://orcid.org/0000-0001-9417-1596
Document Type
Journal Article
Publication Title
Annals of Oncology
PubMed ID
40204154
Publisher
Elsevier
School
School of Medical and Health Sciences
Funders
Melanoma Institute Australia / Burroughs Wellcome Fund / National Health and Medical Research Council / University of Sydney Medical Foundation
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.
DOI
10.1016/j.annonc.2025.03.021
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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., Bagge, R. O., Mattsson, J., Asher, N., Carter, T. J., Meniawy, T. M., . . . Long, G. V. (2025). Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma. Annals of Oncology. Advance online publication. https://doi.org/10.1016/j.annonc.2025.03.021