Exploring the Evolving Scope of Neoadjuvant Immunotherapy in NSCLC

SIMPLE SUMMARY: Immunotherapy with immune checkpoint inhibitors has recently brought a paradigm shift in the treatment of non-small cell lung cancer (NSCLC), but until now, most clinical benefits of immunotherapy have been demonstrated in the setting of advanced or metastatic disease. However, there has been a recent explosion in trial development and research focus exploring whether the benefits of immunotherapy can extend to the neoadjuvant setting for patients with resectable NSCLC. The aim of this review is to thoroughly outline the preclinical rationale for neoadjuvant immunotherapy research. In addition, we summarize and analyze the published interim results as well as results presented at major conferences from the initial early phase trials. An overview of the current and upcoming randomized clinical trials in this field is also provided. Finally, we highlight future challenges and questions that need to be addressed in upcoming research to clarify the role of neoadjuvant immunotherapy in the treatment of NSCLC. ABSTRACT: While lung cancer remains the leading cause of cancer death worldwide, lung cancer mortality has notably decreased in the past decade. Immunotherapy with immune checkpoint inhibitors have played a noteworthy role in contributing to this improved survival, particularly for patients with non-small cell lung cancer (NSCLC). However, until now the benefits have primarily been seen in patients with advanced or metastatic disease. Several recent early phase and ongoing phase III trials have been assessing whether the treatment benefit of immunotherapy in NSCLC can extend to the neoadjuvant setting for resectable diseases. In this comprehensive narrative review, we evaluate the most recent efficacy and safety data from these studies. We also outline questions that will need to be further examined to legitimate neoadjuvant immunotherapy’s role in NSCLC treatment, including the best surrogate marker of response, the incorporation of liquid biopsy for disease monitoring, the ability to be combined with other treatment modalities, the need for further adjuvant therapy, and potential future treatment combinations.