International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 224-234 http://medscipublisher.com/index.php/ijmms 2 24 Meta Analysis Open Access Survival Benefit Analysis of PD-1/PD-L1 Inhibitors Combined with Chemotherapy in Non-Small Cell Lung Cancer Liting Wang Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding email: liting.wang@hibio.org International Journal of Molecular Medical Science, 2025, Vol.15, No.5 doi: 10.5376/ijmms.2025.15.0023 Received: 31 Jul., 2025 Accepted: 03 Sep., 2025 Published: 03 Oct., 2025 Copyright © 2025 Wang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang L.T., 2025, Survival benefit analysis of PD-1/PD-L1 inhibitors combined with chemotherapy in non-small cell lung cancer, International Journal of Molecular Medical Science, 15(5): 224-234 (doi: 10.5376/ijmms.2025.15.0023) Abstract This study explored the survival benefits and clinical significance of PD-1/PD-L1 inhibitors combined with chemotherapy in patients with non-small cell lung cancer (NSCLC). By comprehensively reviewing recent randomized controlled trials and meta-analyses. Compared with chemotherapy alone, the regimen of PD-1/PD-L1 inhibitor combined with chemotherapy significantly prolonged survival and improved disease control rate. The benefit situations of different PD-L1 expression subgroups were consistent. Although the occurrence frequency of immune-related toxicity and chemotherapy-related overlapping toxicity has increased, the overall safety remains within a controllable range. Most serious adverse events can be effectively resolved through early detection and standardized management. In addition, this study also explored the predictive effects of biomarkers such as PD-L1 expression level, tumor mutation burden (TMB), and immune microenvironment characteristics on the therapeutic effect. PD-1/PD-L1 inhibitors combined with chemotherapy in the treatment of non-small cell lung cancer have obvious survival advantages and great clinical potential, providing an important basis for formulating precise immunotherapy regimens. Keywords PD-1/PD-L1 inhibitors; Non-small cell lung cancer (NSCLC); Chemotherapy; Meta-analysis; Immunotherapy 1 Introduction Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases and is the leading cause of cancer-related deaths worldwide. In most regions, the 5-year survival rate has remained relatively low, at only 10%-20%. Because the early symptoms are not obvious, most patients are diagnosed at an advanced stage, which reduces the effect of surgical treatment and ultimately leads to a poor prognosis (Zhao et al., 2025). Although the development of molecular diagnosis and targeted therapy has improved the prognosis of some patients, there are no available driver mutations for many cases of non-small cell lung cancer. Therefore, chemotherapy has become the main treatment option for many patients (Rodak et al., 2021; Jeon et al., 2025). However, the long-term survival benefits brought by traditional chemotherapy and radiotherapy are few, and drug resistance or recurrence in patients is very common (Molina et al., 2008; Tang et al., 2022). The discovery of immune checkpoint pathways, especially PD-1/PD-L1, enables the immune system to recognize and attack tumor cells, completely transforming the way cancer is treated (Fu et al., 2025). Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 have shown significant survival advantages in the treatment of non-small cell lung cancer. Whether used alone or in combination with chemotherapy, they have rapidly become the main treatment options for advanced patients. Important studies such as KEYNOTE-189 and KEYNOTE-407 have shown that adding PD-1/PD-L1 inhibitors to chemotherapy can significantly prolong overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone, and is not related to the expression level of PD-L1 (Tang et al., 2022). Despite these achievements, many problems still exist, such as differences in patient responses, immune-related side effects, and the demand for biomarkers that can predict therapeutic effects in order to better select appropriate patients. This study will explore the survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy for patients with non-small cell lung cancer, and summarize the results of recent randomized controlled trials and meta-analyses. By analyzing the effects of different patient groups and treatment methods, this study will assess
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