DANTE is the largest prospective phase III trial that evaluated the duration of anti-PD-1-based immunotherapy in patients with metastatic melanoma. Although the trial was underpowered due to early closure, stopping treatment after one year appeared non-inferior to continuing for at least two years.
A preferred first-line treatment for patients with unresectable, metastatic melanoma is an immunotherapy regimen including an anti-PD1 antibody, regardless of tumour BRAF mutation status.1 Anti-PD1 antibodies are approved for use until disease progression, and melanoma patients typically receive treatment for at least 24 months.2 Recurrence is rarely seen in patients who respond to treatment beyond two years. The optimal duration of anti-PD1 based immunotherapy has not been established. Reduced treatment duration may reduce risk of long-term side effects and generate cost savings for healthcare systems. At ASCO 2025, results were presented of the DANTE phase III trial evaluating whether one year of first-line anti-PD1 therapy provides outcomes comparable to the standard treatment duration of at least two years in patients with metastatic melanoma.3
DANTE (ISRCTN15837212) is a UK-based, academic, multi-centre, parallel-group, non-inferiority phase III trial. Adult patients with advanced, unresectable stage III or IV melanoma who were receiving first-line anti-PD1 immunotherapy, with or without anti-CTLA-4, were eligible. Patients who remained progression-free after one year of treatment were randomised (1:1) to either continue treatment to at least two years, provided there was no disease progression or unacceptable toxicity, or stop treatment, with the option to restart upon progression. The primary endpoint was progression-free survival (PFS) at one year post-randomisation. Secondary endpoints included quality of life, best objective response, overall survival, safety, and cost-effectiveness.
A total of 415 patients were enrolled, and 166 patients (median age 74 years) were randomised (1:1) to either continue treatment (N= 83) or stop treatment (N= 83). DANTE was closed early due to slow recruitment. Baseline characteristics were generally well balanced between arms, with a slight male predominance (65%). BRAF mutations were present in 26% of randomised patients.
At a median follow-up of 29 months, there were 53 PFS events in total. PFS events occurred in 18 patients in the continued treatment arm (15 due to disease progression and 3 due to death) and in 35 patients in the stop arm (29 due to progression and 6 due to death). At one year post-randomisation, PFS rates were 87.6% with continued treatment and 80.2% in the stop arm (HR[90% CI]: 3.0[1.0-8.5]), with an absolute difference of -7.4%. Complete response was observed in 53% of patients with continued treatment and 45% in the stop arm.
Grade >3 toxicity occurred in 25% of patients with continued treatment and 8% in the stop arm.
DANTE is the largest prospective trial to date assessing the optimal duration of anti-PD1 immunotherapy in patients with metastatic melanoma. Although these results suggest one year of treatment was non-inferior to two years, the trial was underpowered due to early closure. As a result, two years of therapy should remain the standard of care.
References
1. Amaral T, Ottaviano M, Arrance A, et al. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2025;36(1):10-30.
2. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372(26):2521-32.
3. Danson S, Collinson M, Plummer E, et al. Comparison of 1 year versus minimum 2 years of anti-PD1-based immunotherapy as first-line treatment for metastatic melanoma: results of the DANTE phase III trial. Presented at ASCO 2025; Abstract LBA9508.
Top
