Impact of Histology and PD-L1 Status on Immune Checkpoint Inhibitors in the Treatment of Non-Small Cell Lung Cancer a Systemic Review and Meta-analysis.

[INTRODUCTION] Immune checkpoint inhibitors (IO) are widely used in treating advanced non-small cell lung cancer (NSCLC). Historically, patients with squamous cell carcinoma (SCC) had poorer survival than those with nonsquamous (nSCC) histology, but the impact of histology on IO efficacy is underexplored. We conducted a systematic review and meta-analysis to compare survival outcomes between SCC and nSCC NSCLC patients treated with IO.

[METHODS] Following PRISMA guidelines, we searched PubMed, EMBASE, and abstracts from ASCO and ESMO (January 1, 2010-December 31, 2022). Eligible studies were phase II/III randomized controlled trials evaluating IO in NSCLC patients with defined histologic subtypes and available hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS). We pooled HRs to estimate the ratio of HRs (RHR) for OS and PFS. Study quality was assessed using the Cochrane Risk of Bias (RoB) tool.

[RESULTS] Out of 6220 identified records, 23 studies including 14,171 patients were analyzed. No significant differences were observed in OS (RHR 1.06; P = .406) or PFS (RHR 1.09; P = .506) between SCC and nSCC, regardless of therapy line or IO regimen (monotherapy vs. chemo-IO). Subgroup analysis showed no differences based on PD-L1 status. Within each histology, outcomes were also similar between PD-L1+ and PD-L1- patients.

[CONCLUSION] IO efficacy in NSCLC appears independent of histology and PD-L1 status. Although SCC patients previously had worse outcomes, IO therapy may have helped bridge the survival gap between SCC and nSCC patients, by leveraging a shared antitumor immune response mechanism.