PD-1/PD-L1 inhibitors as neoadjuvant therapies in resectable non-small cell lung cancer, including their effects in various PD-1 expression subtypes: A meta-analysis.

Abstract

e20049 Background: The use of PD-1/PD-L1 inhibitors as neoadjuvant agents for resectable non-small cell lung cancer (NSCLC) has shown promising benefits in recent trials and could be a viable treatment option. This study aims to evaluate their overall efficacy as neoadjuvant treatment options and to examine their effects on different PD-1 expression subtypes. Methods: An electronic search was performed using the PubMed, Scopus, and Cochrane databases on December 31, 2024. We included only randomized controlled trials that evaluated PD-1/PD-L1 inhibitors as neoadjuvant or adjuvant therapies, comparing them to chemotherapy in patients with non-small cell lung cancer (NSCLC). The primary endpoints were event-free survival (EFS), pathological complete response (pCR), and overall survival (OS). A subgroup analysis of EFS was conducted based on PD-L1 expression levels (<1, ≥1, 1-49, and ≥50). Effect sizes were calculated using hazard ratios (HR) and odds ratios (OR), both with 95% confidence intervals. A random-effects model was applied. Results: Only four of the 2,551 screened articles met our inclusion criteria, totaling about 3,404 patients. All studies were phase III clinical trials except for two (TD-FOREKNOW and NADIM II). Each trial evaluated the combination of PD-1/PD-L1 inhibitors with chemotherapy, and all of them used chemotherapy monotherapy as the control group. PD-1/PD-L1 inhibitors combination therapy significantly improved event-free survival (EFS) compared to chemotherapy monotherapy, with a hazard ratio of 0.57 (95% CI: 0.51–0.65, p < 0.001). Similarly, overall survival (OS) was significantly improved, with a hazard ratio of 0.64 (95% CI: 0.53–0.77, p < 0.001). Both EFS and OS had low heterogeneity levels (I² = 0). Pathologic complete response (pCR) was significantly higher in the PD-1/PD-L1 combination therapy arm, with an odds ratio of 8.03 (95% CI: 5.33–12.11, p < 0.001), and it had moderate heterogeneity (I² = 49). Finally, in our evaluation of PD-1 expression, all levels had a significant improvement in EFS; even the very low expression subgroup <1 had an HR of 0.76 [0.63, 0.93, p = 0.006, I² = 0]. Conclusions: The use of PD-1/PD-L1 inhibitors in combination with chemotherapy as a neoadjuvant option for patients undergoing surgical resection for NSCLC has demonstrated significant benefits, as evidenced by improvements in EFS, OS, and high pCR rates. Additionally, patients with very low PD-1 expression below one also showed improvements.