Neoadjuvant immunotherapy of locoregionally advanced solid tumors

Abstract

Definitive management of locoregionally advanced solid tumors presents a major challenge and often consists of a combination of surgical, radiotherapeutic and systemic therapy approaches. Upfront surgical treatment with or without adjuvant radiotherapy carries the risks of significant morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of local or distant disease relapse despite the use of standard adjuvant therapy. Preoperative neoadjuvant systemic therapy has the potential to significantly improve clinical outcomes, particularly in this era of expanding immunotherapeutic agents that have transformed the care of patients with metastatic/unresectable malignancies. Tremendous progress has been made with neoadjuvant immunotherapy in the treatment of several locoregionally advanced resectable solid tumors leading to ongoing phase 3 trials and change in clinical practice. The promise of neoadjuvant immunotherapy has been supported by the high pathologic tumor response rates in early trials as well as the durability of these responses making cure a more achievable potential outcome compared with other forms of systemic therapy. Furthermore, neoadjuvant studies allow the assessment of radiologic and pathological responses and the access to biospecimens before and during systemic therapy. Pathological responses may guide future treatment decisions, and biospecimens allow the conduct of mechanistic and biomarker studies that may guide future drug development. On behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group, this article summarizes the current state of neoadjuvant immunotherapy of solid tumors focusing primarily on locoregionally advanced melanoma, gynecologic malignancies, gastrointestinal malignancies, non-small cell lung cancer and head and neck cancer including recent advances and our expert recommendations related to future neoadjuvant trial designs and associated clinical and translational research questions.

Case Report: Durable complete pathologic response and organ preservation following ipilimumab and nivolumab for locally advanced primary vaginal mucosal melanoma

“…To our knowledge, our case is the only published report of a patient with locally advanced vaginal mucosal melanoma experiencing a durable complete pathologic response and organ preservation following immune checkpoint blockade with ipilimumab and nivolumab as the only treatment approach. This case supports future research into neoadjuvant immunotherapeutic strategies to treat locally advanced vaginal mucosal melanoma under multidisciplinary care, early on-treatment assessment for response and close monitoring for immune mediated adverse events ( 27 ).…”

Knowledge mapping of image-guided tumor ablation and immunity: A bibliometric analysis

“…In recent years, cancer immunotherapy has not only been paid more attention by the growing number of researchers, but also has been widely used in clinical practice ( 47 , 48 ). Although a variety of immunotherapy methods are available to treat tumors, including immune checkpoint inhibitors, cytokine, adoptive cell transfer, dendritic cell vaccines and chimeric antigen receptor T cells, immunotherapy based on immune checkpoint inhibitors have become the focus of attention ( 49 , 50 ).…”

Treatment of Stage III Resectable Melanoma—Adjuvant and Neoadjuvant Approaches

“…33,39 Neoadjuvant therapy refers to curative intent treatment, such as systemic therapy, as an upfront induction therapy of cancer before definitive treatment, which is usually surgery (i.e., preoperative therapy). 61 In melanoma, neoadjuvant systemic therapy has the potential to improve the clinical outcomes of stage III patients with clinically evident disease, particularly in this era of expanding immunotherapeutic and targeted agents that have transformed the care of patients with unresectable metastatic disease. Tremendous progress has been made with neoadjuvant systemic therapy in melanoma, as demonstrated by a number of neoadjuvant studies utilizing modern therapeutics that have paved the way for more definitive randomized trials.…”