Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and Parker Center for Cancer Immunotherapy, 885 2nd Avenue, New York, NY 10017, USA.
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and Parker Center for Cancer Immunotherapy, 885 2nd Avenue, New York, NY 10017, USA.
Cancer Cell. 2018 May 14;33(5):853-861.e4. doi: 10.1016/j.ccell.2018.04.001. Epub 2018 May 3.
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks). Efficacy of nivolumab ± ipilimumab was enhanced in patients with high tumor mutational burden. Nivolumab plus ipilimumab appeared to provide a greater clinical benefit than nivolumab monotherapy in the high tumor mutational burden tertile.
免疫检查点抑制剂在小细胞肺癌（SCLC）中显示出持久的应答和令人鼓舞的生存获益，但预测标志物尚不清楚。我们使用全外显子组测序来评估肿瘤突变负担对非随机或随机队列CheckMate 032 中 SCLC 患者接受纳武单抗单药或联合伊匹单抗治疗疗效的影响。患者接受纳武单抗（3mg/kg，每 2 周一次）或纳武单抗联合伊匹单抗（1mg/kg 加 3mg/kg，每 3 周一次，共 4 个周期，随后纳武单抗 3mg/kg，每 2 周一次）。在肿瘤突变负担高的患者中，纳武单抗±伊匹单抗的疗效增强。在肿瘤突变负担高的三分位组中，纳武单抗联合伊匹单抗似乎比纳武单抗单药治疗提供了更大的临床获益。
