Targeted immunocytokines as a neoadjuvant treatment in melanoma

New data recently published on Annals of Oncology showed a significantly longer recurrence-free survival than upfront surgery for a neoadjuvant intralesional targeted immunocytokines treatment in patients with locally advanced melanoma.

The PIVOTAL trial is an open-label, randomized, controlled, multicenter phase III trial involving a total of 246 patients with clinically detectable stage III melanoma; participants were randomized to receive weekly intralesional daromun administrations for 4 weeks before surgery or upfront surgery. At a median follow-up of 21 months, recurrence-free survival was 16.7 months for darumon group and 6.8 months for upfront surgery: the risk of distant recurrence was reduced by 40% in the neoadjuvant arm. Treatment-related adverse effects were more frequent in darumon group but they were moslty injection site reactions. As authors point out, «Neoadjuvant and perioperative immunotherapies are gaining ground in clinical practice for resectable stage III melanoma. Patients who receive neoadjuvant therapy are at risk of losing the opportunity for curative surgery due to disease progression or treatment-related serious adverse events before surgery; however only 4.9% of patients in the neoadjuvant daromun arm experienced disease progression or adverse events leading to inability to undergo surgery, moreover daromun was well tolerated.  In contrast to systemic neoadjuvant regimens, which have reported grade ≥3 adverse events in up to 47% of patients, daromun demonstrated a favorable safety profile with significantly lower rates of high-grade toxicity (28.8%) and serious adverse events (10.2%). Thus neoadjuvant daromun represents a well-tolerated and effective therapeutic option for patients with pretreated, recurrent stage III melanoma. Its favorable safety profile and clinical efficacy support its potential role as a complementary or alternative strategy to systemic immunotherapy, particularly in high-risk patients or those ineligible for immune checkpoint inhibitors».