Abstract：
Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan-Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10-3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00-1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32-3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03-1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41-11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88-16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06-1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04-3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02-1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03-1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.
摘要：
男性非小细胞肺癌（NSCLC）对免疫检查点抑制剂（ICI）单药治疗有更有利的反应，而女性尤其受益于ICI-化疗（CHT）组合。为了阐明临床实践中的这种性别差异，我们回顾性分析了两个接受ICI单药治疗(n=228)或ICI-CHT联合治疗(n=80)治疗晚期NSCLC的队列.Kaplan-Meier分析用于计算无进展生存期（PFS）和总生存期（OS），使用Cox回归分析评估影响变量。在任何一个队列中都没有检测到PFS/OS的显著性别差异。通过东部肿瘤协作组表现状态（ECOG）≥2（风险比（HR）1.90，95％置信区间（CI）：1.10-3.29，p=0.021），较高的C反应蛋白（CRP；HR1.06，95CI：1.00-1.11，p=0.037）和阴性程序性死亡配体1（PD-L1）状态（HR2.04，95CI：1.32-3.15，p=0.001），和OS通过CRP（HR1.09，95CI：1.03-1.14，p=0.002）。在ICI-CHT组合的男性中，多变量分析（MVA）显示鳞状组织学（HR4.00，95CI：1.41-11.2，p=0.009）对PFS有统计学意义；ECOG≥2（HR5.58，95CI：1.88-16.5，p=0.002）和CRP（HR1.19，95CI：1.06-1.32，p=0.002）对OS有统计学意义。在接受ICI单药治疗的女性中，没有变量证明对PFS有意义，而ECOG≥2与OS有显著交互作用(HR1.90,95CI1.04-3.46,p=0.037)。接受ICI-CHT治疗的妇女在PFS（HR1.09，95CI：1.02-1.16，p=0.007）和OS（HR1.11，95CI：1.03-1.19，p=0.004）的CRP方面均有显着的MVA结果。尽管男性和女性对ICI单-和ICI-CHT治疗的反应相似，反应的预测因子因性别而异。
