The role of PD-L1 in patients with non-small cell lung cancer receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy: a meta-analysis

Background: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapy is a promising novel approach in resectable non-small-cell lung cancer (NSCLC). This study aimed to investigate the prognostic value of PD-L1 in patients with NSCLC receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy (CT). Materials and methods: Several databases (PubMed, Embase, and cochrane central register of controlled trials [CENTRAL]) were systematically searched. Randomized controlled trials (RCTs) investigating pathological and survival outcomes with neoadjuvant ICI + CT versus CT alone in NSCLC were analyzed. Results: Overall, eight RCTs (n = 3,404) were included. The analyses showed neoadjuvant ICI + CT significantly improved complete pathological response (pCR) and event-free survival (EFS) in either tumor PD-L1 < 1%, ≥ 1%, 1-49%, or ≥ 50% population (both p < 0.0001) compared with neoadjuvant CT alone. The overall survival (OS) data are not yet mature among all included RCTs, and only three RCTs presented OS data by PD-L1 status of patients. The pooled OS favored neoadjuvant ICI + CT in the PD-L1 ≥ 1% population (hazard ratio [HR], 0.45; 95% CI, 0.31–0.65; p < 0.0001), but not in the PD-L1 < 1% population (HR, 0.89; 95% CI, 0.66–1.19; p = 0.43). Conclusions: Compared with neoadjuvant CT alone, neoadjuvant ICI + CT significantly enhanced pCR and EFS for patients with resectable NSCLC regardless of the expression of PD-L1. It seems that only patients with PD-L1 positive tumors may achieve a better OS, but it's currently inconclusive due to immature data, so future research with long-term follow-up is still needed.