O’Donnell and Hoefsmit et al. argue that neoadjuvant immunotherapy may be superior to adjuvant immunotherapy in combination with surgery. Preclinical and limited clinical evidence supports the hypothesis that inducing an antitumor immune response while the primary tumor mass is present increases the magnitude, breadth, and durability of response, preventing metastatic relapse, though more directly comparable data is needed. The review also addresses the need to optimize treatment timing (to prevent T cell re-exhaustion or surgical delay due to adverse events), agents, and monitoring strategies to maximize long-term clinical response.
Cancer immunotherapies utilizing immune checkpoint inhibitors (ICIs) have demonstrated durable efficacy in a proportion of patients with advanced/metastatic cancers. More recently, the use of ICIs for the adjuvant treatment of patients with surgically resectable melanoma have also demonstrated efficacy by improving relapse-free survival and in the case of ipilimumab (anti-CTLA-4) also improving overall survival. While promising, the effective scheduling of surgery and immunotherapy and its duration is not well elucidated. Recent preclinical studies suggest that surgery followed by adjuvant therapy might be suboptimal as compared to an approach in which immunotherapy is applied before surgery (neoadjuvant immunotherapy). Encouraging findings from early phase clinical trials in melanoma, NSCLC and glioblastoma support the idea that neoadjuvant immunotherapy might have improved clinical efficacy over an adjuvant application. In this review we discuss the existing rationale for the use of neoadjuvant immunotherapy, its apparent strengths, weaknesses, and implications for the design of future clinical trials.