Updated pooled analysis of five-year survival with neoadjuvant therapy in resectable stage IIIB-D melanoma

Neoadjuvant immune checkpoint inhibitors (ICIs) are standard of care for resectable stage IIIB-D melanoma, but knowledge gaps remain regarding optimal treatment type, long-term survival, postsurgical management and clinical, histopathological or molecular subgroups. Pooled analysis from the International Neoadjuvant Melanoma Consortium included 1038 adult patients treated with neoadjuvant ICIs (n=735), BRAF and MEK inhibitors (BRAF/MEKis; n=119), or ICI plus any targeted therapy (ICI+TT; n=184) from 26 centers globally in both trial (n=755; 72.7%) and nontrial (n=283; 27.3%) settings. ICI regimens included anti-PD-1 alone (n=242) and anti-PD-1 plus other immuno-oncology agents (PD1+IO; n=489). Outcomes included major pathologica response (MPR), recurrence-free survival (RFS), and overall survival (OS). An MPR was achieved in 57.8% of patients with ICIs, 51.4% with BRAF/MEKis, and 44.6% with ICI+TT. PD-1+IO elicited higher MPR rates than PD-1 alone (61.4% versus 49.5%). The 5-year RFS rate was 61.0% with PD-1 alone, 73.9% with PD-1+IO, 37.4% with BRAF/MEKis, and 76.4% with ICI+TT; the 5-year OS rates were 83.3%, 87.5%, 69.8%, and 83.9%, respectively. ICI-treated patients with MPR had 5-year OS rates of 98.8% with PD-1 alone and 97.9% with PD-1+IO and gained no benefit from continuing ICIs in the adjuvant setting. The authors conclude that survival outcomes were excellent with neoadjuvant ICIs, particularly in patients achieving MPR, but poor with BRAF/MEKis, and mixed with ICI+TT.