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.

Abstract

LBA9508 Background: Optimal first line therapy for patients with metastatic melanoma is an immunotherapy regimen containing an anti-PD1 antibody, regardless of tumour BRAF mutation status. Anti-PD1 antibodies are licensed for use until disease progression. Recurrence rarely occurs in responding patients after 2 years of treatment. Optimal duration of anti-PD1-based immunotherapy has not been established. Reduced treatment duration may reduce the risk of long-term side-effects and generate cost savings for healthcare systems. Methods: DANTE (ISRCTN15837212) was a UK academic multi-centre parallel group non inferiority trial. Adults with unresectable stage III/IV melanoma receiving first line anti-PD1 +/- anti-CTLA-4 antibody immunotherapy were eligible. Patients who were progression-free after 1 year of treatment were randomised (1:1) to stop treatment (with the option of restarting on progression) or to continue treatment to at least 2 years in the absence of disease progression / unacceptable toxicity (control). The primary endpoint was progression-free survival (PFS) at 1 year post-randomization. Secondary endpoints included quality of life, best objective response, overall survival, toxicity and cost-effectiveness. A qualitative study explored patient acceptance of randomization. Follow-up to 4-years was planned for PFS with secondary outcomes collected up to 18-months post-randomization. Assuming a 2-year PFS rate in the control arm of 86% and defining non-inferiority (NI) as a reduction in PFS of no more than 6%, a sample size of 1208 patients (604 per arm) was required (80% power, 5% significance, 5% drop-out). DANTE closed early due to slow patient enrolment. PFS was compared between arms using Cox’s proportional hazards model, adjusting for stratification factors. Results: Between September 2018 and March 2023, 415 patients were registered from 36 UK hospitals and 166 patients (65.6% male, median age 74, BRAF mutant 25.9%) were randomised. Patient characteristics were broadly balanced. As of 27 th January 2025, with a median follow-up of 29.1 (IQR 17.9-39.3) months, there were 53 PFS events in total: 18 in the control arm (15 progressions+3 deaths) versus 35 in the stop arm (29 progressions+6 deaths). PFS rates at 1-year were 87.6% in the control arm and 80.2% in the stop arm (HR 1.76; 90% CI 1.03-3.03), with an absolute difference of -7.4% and 90% two-sided CI -17.1-2.32, which is within the pre-defined NI margin of 6%. Analyses are ongoing, results for secondary endpoints will be presented. Conclusions: DANTE is the largest prospective melanoma trial evaluating immunotherapy duration completed to date. Although results suggest stopping immunotherapy at 1 year was non-inferior compared to at least 2 years of treatment, the trial was underpowered due to early closure. Continuing immunotherapy for at least 2 years should remain as standard treatment. Clinical trial information: 15837212 .