Medical Oncology Department, Cochin Hospital, AP-HP; Cancer Research for PErsonalized Medicine (CARPEM), Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Cochin Hospital, AP-HP, 75014 Paris, France.
Medical Oncology Department, Cochin Hospital, AP-HP; Cancer Research for PErsonalized Medicine (CARPEM), Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Cochin Hospital, AP-HP, 75014 Paris, France.
EBioMedicine. 2021 Nov;73:103630. doi: 10.1016/j.ebiom.2021.103630. Epub 2021 Oct 20.
Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI.
Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expenditure (REE) was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) provided by the Harris and Benedict formula. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR) based on investigator review per RECIST v1.1. and overall survival (OS). The association of patient's metabolism with 6-month PFS was first explored in a single-center training cohort to estimate the effect size. The relationship between patient's metabolism and 6-month PFS was then tested in an independent non interventional observational prospective cohort (ELY) of 100 patients recruited in two tertiary university centers.
In the entire cohort, the ORR was 14% for the hypermetabolic group (n = 10/74) vs 38% for the normometabolic group (n = 26/68), respectively (estimated difference 25%, 95CI 9-40%, p = 0.001). The DCR was 28% for the hypermetabolic group (n = 21/74) vs 53% for the normometabolic group (n = 36/68), respectively (estimated difference 25%, 95CI 7-42%, p = 0.005). In the validation cohort (100 patients, 2 centers), normometabolic patients (defined as mREE/tREE < 110%) had increased 6-month PFS (57% versus 22%; odds ratio: 4.76; IC95 [1.87 - 12.89]; p<0.001) and improved overall survival (HR 2.20; IC95: 1.41-3.44; p<0.001). The positive and negative predictive values of normometabolism to identify non-progressive patients at 6 months, were 57% and 78% respectively, sensitivity was 72% and specificity was 66%. In multivariate analysis including PD-L1 tumor status, basal metabolism was an independent predictive factor for 6-month PFS.
Normometabolism is a new independent parameter to identify mNSCLC patients who will benefit from ICI, with both improved tumor response, 6-month PFS, and survival.
This work was supported by Baxter (04012016).
免疫检查点抑制剂（ICI）在少数非小细胞肺癌（NSCLC）患者中具有显著疗效。我们在此研究了患者在接受 ICI 治疗期间代谢与结局之间的关系。
转移性 NSCLC 患者在开始免疫治疗前接受营养评估。使用便携式间接测热法测量静息能量消耗（REE）（mREE），并与 Harris 和 Benedict 公式提供的理论值（tREE）进行比较。主要终点为 6 个月无进展生存期（PFS）。次要终点包括根据 RECIST v1.1 由研究者评估的客观缓解率（ORR）和疾病控制率（DCR），以及总生存期（OS）。首先在单中心训练队列中探索患者代谢与 6 个月 PFS 的相关性，以估计效应大小。然后，在两个三级大学中心招募的 100 例患者的独立非干预性前瞻性观察性队列（ELY）中验证患者代谢与 6 个月 PFS 的相关性。
在整个队列中，高代谢组的 ORR 为 14%（n=10/74），而正常代谢组为 38%（n=26/68）（估计差异 25%，95%CI 9-40%，p=0.001）。高代谢组的 DCR 为 28%（n=21/74），而正常代谢组为 53%（n=36/68）（估计差异 25%，95%CI 7-42%，p=0.005）。在验证队列（100 例患者，2 个中心）中，正常代谢组（定义为 mREE/tREE < 110%）的 6 个月 PFS 更高（57% vs 22%；优势比：4.76；95%CI [1.87-12.89]；p<0.001），总生存期也更长（HR 2.20；95%CI：1.41-3.44；p<0.001）。正常代谢组在 6 个月时识别无进展患者的阳性和阴性预测值分别为 57%和 78%，灵敏度为 72%，特异性为 66%。在包括 PD-L1 肿瘤状态的多变量分析中，基础代谢是 6 个月 PFS 的独立预测因素。
正常代谢是识别将从 ICI 中获益的 mNSCLC 患者的新的独立参数，可改善肿瘤反应、6 个月 PFS 和生存。
这项工作得到了百特公司（04012016）的支持。
Zotero 插件