Efficacy and safety of nivolumab plus chemotherapy versus chemotherapy alone for the treatment of advance non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

Abstract

e20576 Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While chemotherapy remains a cornerstone for advanced NSCLC, its significant toxicity limits its use. Combining immunotherapy, such as nivolumab (a PD-1 inhibitor), with chemotherapy may enhance anti-tumor activity through synergistic effects. This systematic review and meta-analysis of checkmate trials to evaluated the efficacy and safety of nivolumab plus chemotherapy versus chemotherapy alone in NSCLC. Methods: This systematic review and meta-analysis compared chemotherapy with or without nivolumab for time-to-event outcomes. PubMed, Embase, and Web of Science were systematically searched. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model (Mantel-Haenszel method). Statistical analysis was performed in RevMan 5.4.1. Results: A total of four checkmate trials were included in this meta-analysis. Nivolumab plus chemotherapy was statistically significant to chemotherapy alone in terms of PFS (Progression Free Survival)(HR 0.64, 95% CI 0.56–0.72; p < 0.00001; I² = 0%). Subgroup analysis for PFS based on various factors demonstrated chemotherapy to be significantly superior in patients with PD-L1 >1%, squamous and non-squamous tumor histology, smoking history, age lower than 65 and ECOG Performance Status 0. Nivolumab plus chemotherapy demonstrated a statistically significant improvement in OS compared to chemotherapy alone (HR 0.77, 95% CI 0.66–0.91; p = 0.002; I² = 6%). Moreover, subgroup analysis of OS revealed chemotherapy to be significantly superior in patients with PD-L1 >50%, squamous histology, smoking history, age under 65 and absence of brain metastasis. In terms of Objective Response Rate (ORR), nivolumab plus chemotherapy was significantly superior to chemotherapy alone (Risk Ratio 1.47, 95% CI 1.19–1.81; p = 0.0003; I² = 53%). The two groups were comparable for Treatment Related Deaths (TRDs) and Treatment Related Adverse Events (TRAEs). Conclusions: Nivolumab plus chemotherapy significantly improves progression-free and overall survival over chemotherapy alone in NSCLC patients, especially those with higher PD-L1 expression and younger ages. Its safety profile is comparable to chemotherapy, with no notable rise in adverse events. Further research is needed to validate these findings across varied patient groups and tumor histologies.