Neoadjuvant daromun improved recurrence-free survival in stage III melanoma

Design

Phase 3 randomised trial, updated analysis at median 36.8 months

Population

256 patients with fully resectable stage III melanoma in the European Union

Primary outcome

Recurrence-free survival (neoadjuvant daromun then surgery vs up-front surgery)

Effect

Recurrence-free survival hazard ratio 0.59 (P = .005); benefit sustained on updated follow-up

The phase 3 PIVOTAL trial randomised 256 patients in the European Union with fully resectable stage III melanoma to neoadjuvant intralesional daromun — a combination of two antibody-cytokine fusion proteins — followed by surgery, or to up-front surgery. It met its primary endpoint, improving recurrence-free survival (hazard ratio 0.59, P = .005), and an updated analysis at a median 36.8 months confirmed the benefit for both recurrence-free and distant metastasis-free survival.

Most enrolled patients (87%) had disease that had recurred after earlier surgery, with or without prior systemic therapy; the remainder were newly diagnosed. A post hoc event-free survival analysis was consistent across subgroups, and no new safety concerns emerged.

This adds an intralesional, skin-directed neoadjuvant option to a melanoma field increasingly built around systemic neoadjuvant immunotherapy. The immediate caveat is access: the trial was conducted in the European Union and the therapy is not available everywhere, so for most Indian patients it is context for referral rather than something to offer now.

• Phase 3, 256 patients, fully resectable stage III melanoma, European Union.
• Neoadjuvant daromun then surgery improved recurrence-free survival: hazard ratio 0.59 (P = .005).
• Benefit held at a median 36.8 months for recurrence-free and distant metastasis-free survival.
• Most patients (87%) had recurrent disease after earlier surgery; no new safety signals.
• Availability is limited to the European Union; treat as context for referral, not routine care here.

Why it matters

It puts a skin-directed, intralesional neoadjuvant option alongside the systemic immunotherapy increasingly used before melanoma surgery.

Don't overread it

This is a single phase 3 trial conducted in the European Union; the event-free survival analysis was post hoc, and the therapy is not widely available.

The statistics, in plain English

A hazard ratio of 0.59 means about a 41 percent lower rate of recurrence over the follow-up; a significant primary endpoint sustained at nearly three years, with consistent event-free survival analyses, makes the benefit reasonably robust for a single trial.

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