Systematic review and meta-analysis of immune checkpoint inhibitors as single agent or in combination with chemotherapy in early-stage non-small cell lung cancer: impact of clinicopathological factors and indirect comparison between treatment strategies

• Published in: European journal of cancer (1990) 2023-12, Vol.195, p.113404-113404, Article 113404
• Main Authors: Nuccio, Antonio, Viscardi, Giuseppe, Salomone, Fabio, Servetto, Alberto, Venanzi, Francesco Maria, Riva, Silvia Teresa, Oresti, Sara, Ogliari, Francesca, Viganò, Mariagrazia, Bulotta, Alessandra, Cameron, Robert, Esposito, Alessandra, Hines, Jacobi, Bianco, Roberto, Reni, Michele, Casconef, Tina, Garassino, Marina Chiara, Torri, Valter, Veronesi, Giulia, Cinquinih, Michela, Ferrara, Roberto
• Format: Article
• Language: English
• Subjects: adjuvant; early-stage; immune checkpoint inhibitors; meta-analysis; neoadjuvant; NSCLC; pCR
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2023.113404

In non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear. Randomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS and OS between neoadjuvant and perioperative strategies. 8 RCTs (2 neoadjuvant, 4 perioperative, 2 adjuvant) (4661 participants) were included. Neoadjuvant/perioperative ICI+PCT significantly improved pCR, EFS, OS, MPR and R0 resection compared to PCT. Adjuvant ICI significantly improved DFS compared to placebo. There was a significant subgroup interaction by PD-L1 status (χ2= 10.72, P = 0.005), pCR (χ2= 17.80, P < 0.0001), and stage (χ2= 4.46, P= 0.003) for EFS. No difference according to PD-L1 status was found for pCR, with 14% of patients having PD-L1 negative tumors still experiencing a pCR. No interaction by PD-L1 status was found for DFS upon adjuvant ICI. Indirect comparison showed no difference in EFS and OS between neoadjuvant and perioperative ICI+PCT. PD-L1 status, pCR and stage impact on survival upon neoadjuvant/perioperative ICI. The restriction of neoadjuvant/perioperative ICI to PD-L1+ patients could preclude pCR and long-term benefit in the PD-L1- subgroup. Neoadjuvant and perioperative could be equivalent strategies. •Neoadjuvant ICI + CT improved pCR, MPR, EFS, OS, R0 resection compared to CT alone.•No subgroup interaction according to PD-L1 was found for pCR in neoadjuvant ICI + CT.•Obtainment of pCR was a predictor of longer EFS: 99% EFS at 1 year.•Stage (III) predicts longer EFS (vs stage I/II) in neoadjuvant/perioperative trials.•Neoadjuvant versusperioperative strategies showed no OS difference by indirect comparison.