ArticleTranslational lung cancer research2025
Comparative effectiveness and safety of systemic therapies for treatment-naïve, PD-L1 expression <1% advanced NSCLC: a systematic review and network meta-analysis.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Metastatic organ distribution characteristics and prognosis in patients with non-small cell lung cancer.Frontiers in medicine · 2026Article
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11 authors.
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Abstract
Background: For advanced non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) expression <1% and no actionable oncogenic alterations, pembrolizumab plus chemotherapy (Pembro-chemo) is widely regarded as the current standard of care. However, emerging therapeutic combinations and preliminary results from ongoing trials challenge its superiority, particularly across different histologic types. Therefore, this study aimed to appraise the effectiveness and safety of first-line treatment for PD-L1 <1% advanced, non-squamous and squamous NSCLC. Methods: PubMed, Ovid Medline, the Cochrane Library, and Embase were searched from database inception to August 15, 2025, to identify phase III randomized controlled trials (RCTs) that explored first-line treatments in treatment-naïve advanced NSCLC, PD-L1 <1%, no epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations; and reported any efficacy outcome were eligible for inclusion. Treatment effectiveness was quantified using overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Surface under the cumulative ranking value (SUCRA) was used to rank the therapies. Risk of bias for included RCTs was assessed using the Cochrane Risk of Bias 2 tool. Results: Twenty-five phase III RCTs involving 5,815 participants were eligible. Overall, 21 first-line treatments were identified. In terms of OS, pembrolizumab + chemotherapy + canakinumab (Pembro-chemo-canakinumab) (SUCRA =0.90) showed great potential in improving outcomes, although its long-term efficacy still needed to be validated. Nivolumab + ipilimumab (Nivo-ipi) (SUCRA =0.78) closely followed. Both top regimens showed non-significant superiority over Pembro-chemo. Regarding PFS, nivolumab + chemotherapy + bevacizumab (SUCRA =0.88), and serplulimab + chemotherapy (SUCRA =0.87) were the optimal regimens. Specifically for non-squamous patients, Pembro-chemo was optimal for OS (SUCRA =0.90), followed by Nivolumab + chemotherapy + bevacizumab (SUCRA =0.82). Nivolumab + chemotherapy + bevacizumab optimized PFS, with an hazard ratio (HR) of 0.52 [95% confidence interval (CI): 0.30-0.92 Conclusions: First-line personalized treatment for PD-L1 <1%, advanced NSCLC should be histology-based, balancing efficacy and toxicity. Pembro-chemo and nivolumab + chemotherapy + bevacizumab combinations are recommended as the optimal first-line options for non-squamous patients, and Nivo-ipi-chemo for squamous patients.
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