Neoadjuvant immunotherapy for non–small cell lung cancer: State of the art

Abstract

Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy. Immune checkpoint inhibitors (ICIs) have rapidly evolved from investigational drugs to standard of care for the treatment of metastatic non‐small cell lung cancer (NSCLC). In particular, antibodies that block inhibitory immune checkpoints, such as programmed cell death protein 1 (PD‐1) and programmed cell death 1 ligand 1 (PD‐L1), have revolutionized the treatment of advanced NSCLC, when administered alone or in combination with chemotherapy. Immunotherapy is associated with higher response rates, improved overall survival (OS), and increased tolerability compared with conventional cytotoxic chemotherapy. These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC. Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long‐term OS or cure rates in resectable NSCLC. Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC. In addition, we discuss several unresolved challenges, including the evaluations to assess neoadjuvant immunotherapy response, the role of adjuvant treatment after neoadjuvant immunotherapy, the efficacy of treatment for oncogenic‐addicted tumors, and predictive biomarkers. We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.

Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC)

“…Patients with non-small-cell lung cancer (NSCLC) most often present with inoperable, locally advanced or metastatic disease for which no cure is available [2,3]. Although survival has improved significantly in recent years with the introduction of kinase inhibitors and immune checkpoint inhibitors, the 5-year survival rate is still only about 25% [1,4,5]. The standard of care for patients with NSCLC varies with the stage of the disease at diagnosis [6].…”

Increased Tumor Growth Rate and Mesenchymal Properties of NSCLC-Patient-Derived Xenograft Models during Serial Transplantation

“…Despite progress in the use of targeted therapies, the optimism arising from their application has been tempered by inconsistent responses to these therapies and the emergence of drug resistance in many patients [4]. Progress in SCC treatments has been modest, and targeted therapy in this disease has not yet been proven successful [8,9].…”

Immune Checkpoint Inhibitors in Advanced NSCLC: [18F]FDG PET/CT as a Troubleshooter in Treatment Response

“…Interestingly, in the multivariate analysis, it was shown that immunotherapy employed as a second or more line of therapy was significantly correlated to a better response rate. We can speculate that this finding could be associated with the growing evidence that cytotoxic chemotherapy and radiotherapy could impact tumor ligand expression, determining changes in cell PD-L1 expression as well as in the tumor microenvironment [ 21 , 22 ].…”