Department of Oncology and Hematology, AUSL Romagna, Ravenna, Italy.
Fondazione Ricerca Traslazionale, Rome, Italy.
J Immunother Cancer. 2019 Nov 21;7(1):316. doi: 10.1186/s40425-019-0793-8.
Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy.
Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM.
Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p < 0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p < 0.0001; Cohort B: 2.7 versus 5.2 months, p < 0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p < 0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78).
BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.
骨转移（BoM）是非小细胞肺癌（NSCLC）的一个负面预后因素。除了支持作用外，骨骼还是一个活跃调节免疫系统的造血器官。我们假设 BoM 可能会影响免疫疗法的敏感性。
根据 BoM 评估了意大利扩大准入计划中包含的预处理非鳞状（队列 A）和鳞状（队列 B）NSCLC 对纳武利尤单抗疗效的影响。
队列 A 包括 1588 名非鳞状 NSCLC 患者，其中 626 名（39%）有 BoM（BoM+），962 名（61%）无 BoM（BoM-）。队列 B 包括 371 名鳞状组织学患者，其中 120 名 BoM+（32%）和 251 名 BoM-（68%）。BoM+的总缓解率（ORR；队列 A：12%比 23%，p<0.0001；队列 B：13%比 22%，p=0.04）、无进展生存期（PFS；队列 A：3.0 比 4.0 个月，p<0.0001；队列 B：2.7 比 5.2 个月，p<0.0001）和总生存期（OS；队列 A：7.4 比 15.3 个月，p<0.0001；队列 B：5.0 比 10.9 个月，p<0.0001）均较低。此外，BoM 不论表现状态（PS；两个队列的 OS：p<0.0001）和肝转移（队列 A 的 OS：p<0.0001；队列 B 的 OS：p=0.48）如何，都对结局产生负面影响。多变量分析显示，BoM 与死亡风险增加独立相关（队列 A：HR 1.50；队列 B：HR 1.78）。
BoM 会损害免疫疗法的疗效。在免疫治疗临床试验中应纳入准确的骨骼分期。
