AUTHOR=Zhang Feiyang , Chen Guoming , Yin Yixin , Chen Xiaojiang , Nie Runcong , Chen Yingbo 

TITLE=First-line immune checkpoint inhibitors in low programmed death-ligand 1-expressing population

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1377690

DOI=10.3389/fphar.2024.1377690

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Inhibitors of programmed cell death 1 (PD1) and its ligand (PDL1) have exhibited favorable long-term survival in many types of advanced-stage cancer and current approvals have to date been granted in certain tumour types irrespective of PD-L1 status.</p><p><bold>Methods:</bold> We extracted the following information: study sample size, trial period, cancer types, intervention of treatment, type of PD-L1 antibody, immunohistochemistry (IHC) scoring method, number and percentage of PD-L1 &lt; 1% population, and median follow- up time. PD-L1 expression was defined as percentage of number of PD-L1-stained tumor cells (TPS), area of tumor infiltrated by PD-L1-stained immune cells (IPS), number of PD-L1-stained cells (tumor cells, lymphocytes and macrophages; CPS). Different trials used distinct method to define low PD-L1 expression. The risk of bias of the included trials was assessed by using the Cochrane risk of bias tool for RCTs.</p><p><bold>Results:</bold> Here, a total of 34 trials were included to extract individual patient data (IPD) to evaluate the survival benefit of first line PD1/PDL1 inhibitors vs. standard-of-care (SOC) in patients with PDL1 &lt; 1%. In term of anti-PD-1/PD-L1 monotherapy, OS (HR = 0.90, 0.81−1.01) and PFS (HR = 1.11, 0.97−1.27) between PD-1/PD-L1 inhibitor group and SOC group were comparable. In term of anti-PD-1/PD-L1 combination therapy, PD-1/PD-L1 inhibitor group exhibited longer OS (median 19.5 months vs. 16.3 months; HR = 0.83, 0.79−0.88, <italic>p</italic> &lt; 0.001) and PFS than those of SOC group (median 8.11 months vs. 6.96 months; HR = 0.82, 0.77−0.87, <italic>p</italic> &lt; 0.001).Subgroup analysis showed that survival benefit was mainly observed in non-small cell lung cancer (NSCLC) (HR<sub>OS</sub> = 0.74; HR<sub>PFS</sub> = 0.69; <italic>p</italic> &lt; 0.001), small-cell lung cancer (SCLC) (HR<sub>OS</sub> = 0.58, <italic>p</italic> &lt; 0.001; HR<sub>PFS</sub> = 0.55, <italic>p</italic> = 0.030), esophageal squamous cell carcinoma (ESCC) (HR<sub>OS</sub> = 0.62, <italic>p</italic> = 0.005; HR<sub>PFS</sub> = 0.79, <italic>p</italic> &lt; 0.001), melanoma (HR<sub>OS</sub> = 0.53, <italic>p</italic> &lt; 0.001) and nasopharyngeal carcinoma (NPC) (HR<sub>PFS</sub> = 0.35, <italic>p</italic> = 0.013).</p><p><bold>Conclusion:</bold> Anti-PD-1/PD-L1 combinational therapy rather than monotherapy exhibit survival benefit in the low PD-L1 population in the first-line setting, and the survival benefit was mainly observed in specific tumor types.</p>