Critical reviews in oncology/hematology · 2025
Comparative efficacy of first-line therapies for PD-L1-negative advanced NSCLC: A network meta-analysis with reconstructed survival curves.
СтатьяСистематический обзорСравнительное исследованиеNetwork Meta-AnalysisНазвание и аннотация: Перевод пока не подготовлен
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Ma Jie-Tao, Yang Mei-Qi, Zhang Shu-Ling, Huang Le-Tian, Sun Li, Han Cheng-Bo
Аннотация
OBJECTIVES: The optimal first-line treatment for programmed death-ligand 1 (PD-L1)-negative advanced non-small cell lung cancer (NSCLC) without actionable mutations remains uncertain. Histological subtype-driven strategies may enhance outcomes in this population.
METHODS: We conducted a systematic review and network meta-analysis (NMA) of 24 randomized controlled trials involving 5035 patients with PD-L1-negative advanced NSCLC. Survival curves were reconstructed (SCR) using WebPlotDigitizer. Analyses were performed using R and Stata.
RESULTS: Ten treatment regimens were evaluated. For histology-unselected NSCLC, anti-PD-1 + chemotherapy (CT) ranked highest for objective response rate (94.7 %) and progression-free survival (PFS; 89.3 %; HR = 0.63, 95 % CI: 0.56-0.71 vs. CT), while anti-PD-1 + anti-CTLA-4 ranked highest for duration of response (94.9 %) and overall survival (OS; 85.9 %; HR = 0.65, 95 % CI: 0.51-0.83 vs. CT). Indirect comparisons and SCR analyses showed comparable PFS and OS between anti-PD-1 + anti-CTLA-4 and anti-PD-1 + CT. In non-squamous NSCLC, bevacizumab + anti-PD-(L)1 + CT achieved the longest median PFS (10.02 months) and OS (28.88 months). For squamous NSCLC, anti-PD-1 + CT significantly improved PFS (HR = 0.58, 95 % CI: 0.50-0.68) and OS (HR = 0.71, 95 % CI: 0.57-0.88) versus CT, while anti-PD-L1 + CT showed no significant benefit (PFS: HR = 0.81; OS: HR = 0.87; P > 0.05).
CONCLUSIONS: Dual immunotherapy and anti-PD-1 + CT provide comparable survival benefits in PD-L1-negative, histology-unselected NSCLC. Histology-driven strategies-bevacizumab-containing regimens for non-squamous and anti-PD-1 + CT for squamous NSCLC-are associated with optimized outcomes, supporting personalized treatment by subtypes.
METHODS: We conducted a systematic review and network meta-analysis (NMA) of 24 randomized controlled trials involving 5035 patients with PD-L1-negative advanced NSCLC. Survival curves were reconstructed (SCR) using WebPlotDigitizer. Analyses were performed using R and Stata.
RESULTS: Ten treatment regimens were evaluated. For histology-unselected NSCLC, anti-PD-1 + chemotherapy (CT) ranked highest for objective response rate (94.7 %) and progression-free survival (PFS; 89.3 %; HR = 0.63, 95 % CI: 0.56-0.71 vs. CT), while anti-PD-1 + anti-CTLA-4 ranked highest for duration of response (94.9 %) and overall survival (OS; 85.9 %; HR = 0.65, 95 % CI: 0.51-0.83 vs. CT). Indirect comparisons and SCR analyses showed comparable PFS and OS between anti-PD-1 + anti-CTLA-4 and anti-PD-1 + CT. In non-squamous NSCLC, bevacizumab + anti-PD-(L)1 + CT achieved the longest median PFS (10.02 months) and OS (28.88 months). For squamous NSCLC, anti-PD-1 + CT significantly improved PFS (HR = 0.58, 95 % CI: 0.50-0.68) and OS (HR = 0.71, 95 % CI: 0.57-0.88) versus CT, while anti-PD-L1 + CT showed no significant benefit (PFS: HR = 0.81; OS: HR = 0.87; P > 0.05).
CONCLUSIONS: Dual immunotherapy and anti-PD-1 + CT provide comparable survival benefits in PD-L1-negative, histology-unselected NSCLC. Histology-driven strategies-bevacizumab-containing regimens for non-squamous and anti-PD-1 + CT for squamous NSCLC-are associated with optimized outcomes, supporting personalized treatment by subtypes.