Background and Importance Immune checkpoint inhibitors (ICIs) are currently part of the standard treatment of non-small-cell lung cancer (NSCLC) in the context of adjuvant therapy. However, its use in neoadjuvant therapy (NAT), although relatively more recent, has encouraging potential.

Aim and Objectives To evaluate the efficacy of ICIs-based NAT in the early stages of lung cancer.

Material and Methods A systematic review was carried out through Medline, for articles published until August 2023.

The methods used were based the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for phase-2/3 randomised clinical trials (RCTs) that evaluated the efficacy of NAT with ICIs both in monotherapy and in combination with chemotherapy NSCLC in stages I-III.

Two reviewers independently assessed the eligibility of each study. To evaluate their quality, the Grades scale was used.

Results 10 studies met the inclusion criteria: two were phase 3, six used PD-1 inhibitors and four used PD-L1 inhibitors. Moreover, three studies continued adjuvant treatment with ICIs.

NADIM trial studied nivolumab+chemotherapy before surgery and obtained a progression-free survival (PFS) of 77.1% and a pCR rate of 63.4%. Subsequently, in NADIM II, patients were randomised to receive nivolumab+chemotherapy or chemotherapy alone, showing a better pCR rate (36.2% vs 6.8%) and better PFS with nivolumab.

In CheckMate 816, nivolumab+chemotherapy resulted in a higher median event-free supervenience (EFS) than chemotherapy alone (31.6 vs. 20.8 months) as well as a higher pCR rate.

The NEOSTARstudy showed a higher pCR rate of the nivolumab+ipilimumab combination compared to nivolumab monotherapy Other studies, such as Shue et al. using atezolizumab+chemotherapy, or LCMC3, also supported the efficacy of neoadjuvant immunotherapy (NAIT), with improvements in response rates.

KEYNOTE 671 evaluated pembrolizumab+chemotherapy showing better EFS and RCp in the pembrolizumab group compared to placebo use.

Finally, PRINCESS and IONESCO studied the use of atezolizumab and durvalumab, respectively, and did not provide favourable results.

Conclusion and Relevance These studies support the use of NAIT in patients with resectable NSCLC, with promising results in terms of survival and pCR. Currently, nivolumab is used in resectable lung cancer according to CheckMate 816.

Conflict of Interest No conflict of interest.