Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials
Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials
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DOI：
10.1016/j.annoc.2020.01.006
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发表时间：
2020-04-01
影响因子：
50.5
通讯作者：
Herrera, F. G.
中科院分区：
文献类型：
--
作者：
Chalabi, M.;Cardona, A.;Herrera, F. G.
背景资料：临床前数据表明，质子泵抑制剂（PPI）可以调节微生物组，单臂研究表明抗生素（ATB）可能会降低免疫检查点抑制剂（ICI）的疗效，但缺乏随机对照试验数据。该汇总分析评估了ATB和PPI对随机分配至ICI和化疗组的患者结局的影响。该回顾性分析使用了来自II期白杨的汇总数据（NCT 01903993）和第10阶段OAK（NCT 02008227）试验，纳入1512例既往接受过治疗的非小细胞肺癌（NSCLC）患者，随机分配接受atezolizumab（n = 757）或多西他赛（n = 755）。本分析的主要目的是评估ATB和PPI使用对总生存期（OS）和无进展生存期（PFS）的影响。结果：atezolizumab组和多西他赛组分别有169例（22.3%）和202例（26.8%）患者接受ATB治疗，234例（30.9%）和260例（34.4%）患者接受PPI治疗。所有患者的多变量分析显示，ATB与OS较短相关[风险比（HR）1.20，95%置信区间（CI）1.04-1.39]，PPI也是如此（HR 1.26，95% CI 1.10-1.44）。在atezolizumab人群中，接受ATB（8.5 vs 14.1个月，HR 1.32，95% CI 1.06-1.63，P = 0.01）或PPI（9.6 vs 14.5个月，HR 1.45，95% CI 1.20-1.75，P = 0.0001）治疗的患者的OS显著缩短。在atezolizumab人群中，PPI使用与PFS缩短相关（1.9 vs 2.8个月，HR 1.30，95% CI 1.10-1.53，P = 0.001）。ATB和PPI的使用和PFS或OS之间没有关联多西他赛population.Conclusion：在这两个随机试验的计划外分析，数据表明，ATB或PPI的使用与转移性NSCLC患者的预后不良，可能会影响ICI的疗效。
Background: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy.Patients and methods: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase 10 OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS).Results: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population.Conclusion: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.