Immunotherapy for Stage III Melanoma: Neoadjuvant vs. Adjuvant
Posted: Thursday, November 8, 2018
A Dutch/American research team found that neoadjuvant ipilimumab plus nivolumab expanded more tumor-resident T-cell clones in patients with phase III palpable melanoma than did adjuvant treatment. The results of the 20-patient, randomized, phase Ib feasibility trial were published in Nature Medicine. Two benefits of neoadjuvant therapy are that it can determine therapeutic efficacy within the individual patient for possible adjuvant therapy, if needed, and reduce the tumor burden before surgery.
Low-tumor T-cell infiltration is associated with relapse, so the neoadjuvant regimen “appears promising,” wrote lead author Christian U. Blank, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and colleagues, with seven of nine patients in the neoadjuvant arm achieving a pathologic response. None had relapsed after a median follow-up of 25.6 months. However, 90% of patients in both arms “experienced one or more grade 3/4 adverse events,” suggesting “further investigation [should address ways] to preserve efficacy but reduce toxicity,” noted the researchers.
In this study, patients in the adjuvant arm received ipilimumab and nivolumab as four courses after surgery; the neoadjuvant regimen included two courses each before and after surgery. “OpACIN is the first trial comparing neoadjuvant with adjuvant immune checkpoint combination therapy, demonstrating a high clinical activity of neoadjuvant therapy, and possible superiority of neoadjuvant treatment, as based on immunomonitoring,” concluded Dr. Blank and colleagues. However, they added, toxicity was “higher than expected, arguing for the development of reduced-intensity regimens in this disease setting.”