高骨肿瘤负荷可识别晚期非小细胞肺癌患者，通过骨靶向药物和免疫检查点抑制剂获得生存获益。
High bone tumor burden to identify advanced non-small cell lung cancer patients with survival benefit upon bone targeted agents and immune checkpoint inhibitors.
发表日期：2023 Oct 29
作者：
Sara Manglaviti, Marta Bini, Giulia Apollonio, Ernesto Zecca, Giulia Galli, Sabina Sangaletti, Alice Labianca, Elisa Sottotetti, Marta Brambilla, Mario Occhipinti, Claudia Proto, Arsela Prelaj, Diego Signorelli, Alessandro De Toma, Giuseppe Viscardi, Teresa Beninato, Laura Mazzeo, Achille Bottiglieri, Rita Leporati, Giuseppe Fotia, Monica Ganzinelli, Paola Portararo, Marina Chiara Garassino, Filippo G M de Braud, Giuseppe Lo Russo, Valter Torri, Roberto Ferrara
来源：
LUNG CANCER
摘要：
骨靶向药物（BTA），如地诺塞麦（DN）和唑来膦酸（ZA），历来可降低骨转移（BM）癌症患者骨骼相关事件的风险，但生存结果没有改善。在免疫治疗时代，BM 与免疫检查点抑制剂 (ICI) 的不良预后相关。目前，骨肿瘤负荷对接受 ICI 治疗的晚期非小细胞肺癌 (aNSCLC) 患者的 BTA 生存的影响仍不清楚。来自接受 ICI 治疗的 BM 的 aNSCLC 患者的数据 (4/2013-5/2022) 在一项研究中机构进行回顾性收集。 BTA-ICI 同步治疗被定义为在 ICI 开始之前或之后 90 天内的任何时间施用 BTA。高骨肿瘤负荷 (HBTB) 定义为 ≥ 3 个 BM 部位。中位 OS (mOS) 使用 Kaplan-Meier 进行估计。 Aikaike 信息标准 (AIC) 用于选择根据临床变量调整的数据分析的最佳模型。在 134 名患者中，51 名 (38%) 接受了 BTA。 mFU 为 39.6 个月 (m) 时，BTA-ICIs 并行治疗对 mOS 没有显着影响 [8.3 m (95% CI 3.9-12.8) 对比 (vs) 6.8 m (95% CI 4.0-9.6) p = 0.36] ;这些结果在对 AIC 选择的临床变量进行调整后得到证实。多变量模型显示 BTA 的使用与 HBTB 或 BM 放射治疗之间存在显着的相互作用。在亚组分析中，只有 HBTB 被证实与显着延长的 mOS [8.3 m (95% CI 2.4-14.2) vs 3.5 m (95% CI 2.9-4.1)，p = 0.003] 和 mPFS [3.0 m (95% CI) BTA-ICI 同步治疗时，[1.6-4.4) vs 1.8 m (95% CI 1.6-2.0) p = 0.001]，DN-ICI 同步治疗方案观察到最明显的 OS 获益 [15.2 m (95% CI 0.1-30.7) vs 3.5 m (95% CI 2.9-4.1) p = 0.002]。在免疫治疗时代，HBTB 可以识别 BTA 带来生存获益的患者，尤其是 DN-ICI 组合。 HBTB 应作为分层因素纳入即将开展的评估 BTA 和 ICI 组合治疗 aNSCLC 和 BM 患者的试验中。版权所有 © 2023 Elsevier B.V. 保留所有权利。
Bone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown.Data from ICI-treated aNSCLC patients with BM (4/2013-5/2022) in one institution were retrospectively collected. BTA-ICI concurrent treatment was defined as BTA administration at any time before or within 90 days from ICI start. High bone tumor burden (HBTB) was defined as ≥ 3 sites of BM. Median OS (mOS) was estimated with Kaplan-Meier. Aikaike's information criterion (AIC) was used to select the best model for data analysis adjusted for clinical variables.Of 134 patients included, 51 (38 %) received BTA. At a mFU of 39.6 months (m), BTA-ICIs concurrent treatment did not significantly impact on mOS [8.3 m (95% CI 3.9-12.8) versus (vs) 6.8 m (95% CI 4.0-9.6) p = 0.36]; these results were confirmed after adjustment for clinical variables selected by AIC. A multivariate model showed a significant interaction between BTA use and HBTB or radiation therapy to BM. In subgroup analyses, only HBTB confirmed to be associated with significantly longer mOS [8.3 m (95% CI 2.4-14.2) vs 3.5 m (95% CI 2.9-4.1), p = 0.003] and mPFS [3.0 m (95% CI 1.6-4.4) vs 1.8 m (95% CI 1.6-2.0) p = 0.001] upon BTA-ICI concurrent treatment, with the most pronounced OS benefit observed for DN-ICI concurrent regimen [15.2 m (95% CI 0.1-30.7) vs 3.5 m (95% CI 2.9-4.1) p = 0.002].In the immunotherapy era, HBTB can identify patients experiencing survival benefit with BTA, especially with DN-ICI combination. HBTB should be included as a stratification factor in the upcoming trials assessing BTA and ICI combinations in patients with aNSCLC and BM.Copyright © 2023 Elsevier B.V. All rights reserved.