One Year or Two? DANTE Trial Explores Immunotherapy Duration in Metastatic Melanoma

Optimal first-line therapy for metastatic melanoma includes immunotherapy with anti-PD-1 therapies, which are continued until progression of disease or toxicity. But patients with disease that responds to treatment rarely have recurrence after two years on therapy. Immunotherapy costs, patient burden, and long-term immune-related adverse events all fuel interest in treatment de-escalation strategies.

Could one year of anti-PD-1 immunotherapy achieve similar clinical outcomes as continuation of therapy for two or more years? The DANTE phase III trial, the largest of its kind to date, sought to examine anti-PD-1 treatment duration in this population.

Trial Design: Shortened Therapy vs. Standard Duration

The UK-led, multicenter, non-inferiority trial enrolled patients with unresectable stage III/IV melanoma receiving first-line anti-PD-1 therapy, with or without anti-CTLA-4. Patients who remained progression-free after one year of treatment were then randomized to either:

• Stop therapy (with re-initiation allowed upon progression), or
• Continue treatment to a minimum of two years (control arm).

The primary endpoint was progression-free survival (PFS) at one year post-randomization.

Key Findings: Marginal PFS Difference Within Non-Inferiority Margin

Below is a recap of the results:

• 166 patients were randomized (median age 74, 65.6 percent male, 25.9 percent BRAF-mutant).
• At a median follow-up of 29.1 months, 53 PFS events occurred:
• Stop arm: 29 progressions + 6 deaths
• Continuation arm: 15 progressions + 3 deaths
• One-year PFS was:
• Stop arm: 80.2 percent
• Continuation arm: 87.6 percent
• The hazard ratio for PFS was 1.76 (90 percent CI: 1.03–3.03), an absolute difference of -7.4 percent (90 percent CI: -17.1 to 2.32)

Clinical Interpretation: Cautious Endorsement of Standard Duration

Although the absolute difference in one-year PFS fell within the study’s pre-specified non-inferiority margin of 6 percent, the trial closed early due to slow enrollment, limiting the ability to conclusively establish equivalence.

While these findings suggest that stopping at one year may be viable for select patients if needed, such as those with durable disease control and concern over cumulative toxicity, continuing treatment for at least two years remains the evidence-backed standard. This is especially relevant in the absence of predictive biomarkers to identify optimal discontinuation candidates.

Context and Implications

The DANTE trial addresses the pressing issue of evidence-based de-escalation strategies in oncology: how to optimize treatment duration to reduce toxicity and cost without compromising clinical outcomes.

With the trial’s premature closure, which was possibly affected by patient and clinician reluctance to alter successful therapy regimens, continuing anti-PD-L1 therapy until progression of disease remains the benchmark in first-line metastatic melanoma treatment. But data from DANTE opens the door to collect further evidence examining individualized duration strategies grounded in patient preference, tolerability, and clinical trajectory.

Reference:
Danson S, Collinson M, Plummer E, Ottensmeier C, Silva S, Hook J, et al. LBA9508: 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 presented at American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2025. Chicago, IL.