International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 224-234 http://medscipublisher.com/index.php/ijmms 2 29 that the advantages of OS and PFS could be sustained, and some patients achieved long-term disease control for more than two years. Real-world cohort studies further verified these findings, showing that the higher the PD-L1 tumor proportion score (TPS), the better the OS and PFS in the real world. However, even patients with TPS≤1% can benefit from combination therapy. However, the effect was not as good as that of patients with higher TPS. Figure 2 Forest plots of HR of PFS/OS for PD-1/PD-L1 inhibitors in the intention-to-treat population (Adopted from Wankhede et al., 2022) Some real data also emphasize the importance of early assessment of treatment response and point out that for patients with low PD-L1 expression and no response to initial treatment, other treatment options need to be considered (Faghmous et al., 2025). These results further demonstrate the clinical value of chemotherapy combined with immunotherapy, and also illustrate the ongoing importance of individualized treatment in the management of non-small cell lung cancer. 6 Safety and Adverse Reactions 6.1 Characteristics of Immune-related Adverse events Immune-related adverse events (irAEs) are a specific type of toxic reaction of PD-1/PD-L1 inhibitors, which occur when the immune system is activated and attacks normal tissues. Among patients with non-small cell lung cancer, approximately 22% to 30% will develop irAEs. The most vulnerable organs include endocrine glands (such as the thyroid), lungs (causing pneumonia), musculoskeletal system, colon, liver and skin (Chen et al., 2023). Most irAEs are mild to moderate (grade 1-2), but about 4%-11% will develop into severe (grade 3-4), and a few cases (<1%) may be fatal, especially myocarditis and pneumonia. irAEs usually occur in the first few months after the start of treatment, but the time of occurrence varies among different organ systems. It should be noted that in patients with non-small cell lung cancer receiving immunotherapy, if irAEs (especially those related to multiple systems or skin) occur, the progression-free survival and overall survival of the patients will be longer, indicating an association between immune system activation and therapeutic effect (Shankar et al., 2020) However, some irAEs, such as those with severe pneumonia or requiring high-dose steroid treatment, may have adverse effects on survival, which also emphasizes the importance of assessing specific organ risks (Chen et al., 2023).
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