BackgroundWhile immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non‐small‐cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long‐lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre‐treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first‐line pembrolizumab monotherapy for advanced NSCLC.MethodsA retrospective review of consecutive patients with treatment‐naïve NSCLC and PD‐L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre‐treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre‐established cut‐offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression‐free survival and overall survival (PFS and OS), compared through the log‐rank test and the Cox proportional hazards model.ResultsData from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69 years (range 36–85), with a median follow‐up of 12 months (range 1–131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co‐morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46–12.6, P < 0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22–2.83, P = 0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P < 0.0001 and 30.7% vs. 73.2%, P < 0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co‐morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60–4.66, P < 0.0001; sarcopenia: aHR 2.24, 95% CI 1.37–3.67, P = 0.001; IMAT depot: aHR 2.26, 95% 1.40–3.63, P = 0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96–6.01, P < 0.0001; sarcopenia: aHR 4.68, 95% CI 2.44–8.99, P < 0.0001; IMAT depot: aHR 3.18, 95% 1.72–5.88, P < 0.0001).ConclusionsSkeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers.

中文翻译：

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一线 pembrolizumab 治疗肺癌患者的体成分紊乱：一项多中心观察性研究


背景虽然免疫检查点抑制剂 （ICI） 正在日益重塑非小细胞肺癌 （NSCLC） 的治疗格局，但只有有限比例的患者通过这些治疗获得相关且持久的益处，因此需要确定临床疗效的预测因子，理想情况下是可改变的预测因子。身体成分表型可能反映了患者免疫学的各个方面，从而反映了他们对 ICI 的反应能力。本研究旨在探讨接受一线 pembrolizumab 单药治疗晚期 NSCLC 的患者治疗前体成分表型、肿瘤反应和临床结果之间的可能关联。方法对连续的初治 NSCLC 和 PD-L1 表达患者进行了回顾性评价 ≥50% 在 3 个学术机构接受 pembrolizumab。通过计算机断层扫描在第三腰椎水平测量治疗前的身体成分参数，使用预先设定的临界值定义。主要终点是客观缓解率 （ORR） 、次要终点无进展生存期和总生存期 （PFS 和 OS），通过对数秩检验和 Cox 比例风险模型进行比较。结果收集了 134 例患者 （93 例男性 [69.4%] 和 41 例女性 [30.6%] 的数据。中位年龄为 69 岁 （范围 36-85），中位随访 12 个月 （范围 1-131）。中位体重指数 （BMI） 为 24.5 （IQR 21.5;26.1） kg/m2。总体而言，59.0% 和 51.5% 的患者分别符合肌肉减少症和肌脂肪变性证据的既定影像学标准，这两种情况发生在 BMI 范围内。根据合并症进行调整的多变量回归分析显示，肌肉减少症 （aOR 5.56,95% CI. 2.46–12.6，P < 0.0001） 和低肌间脂肪组织 （IMAT） 面积 （aOR 1.83,95% CI. 1.22–2.83，P = 0.001） 与较低的 ORR 率相关 （分别为 30.4% vs. 70.5%，P < 0.0001 和 30.7% vs. 73.2%，P < 0.0001）。此外，在单变量和多变量分析中，根据合并症进行调整，根据东部肿瘤合作组量表 （ECOG PS） 调整的低体能状态、肌肉减少症和低 IMAT 与短 PFS 显著相关（ECOG PS：aHR 2.73,95% CI 1.60-4.66，P < 0.0001;肌肉减少症：aHR 2.24,95% CI 1.37-3.67，P = 0.001;IMAT 仓库：aHR 2.26,95% 1.40-3.63，P = 0.002）和 OS（ECOG PS：aHR 3.44,95% CI 1.96-6.01，P < 0.0001;肌肉减少症：aHR 4.68,95% CI 2.44-8.99，P < 0.0001;IMAT 仓库：aHR 3.18,95% 1.72–5.88，P < 0.0001）。结论骨骼肌异常在 NSCLC 中明显常见，可能代表对 ICI 反应和生存结果的有趣预测标志物。需要大型前瞻性试验来验证 ICIs 反应者的临床生物标志物。