Shieh Kevin R, Huang Anna, Xu Yiqing
Department of Medicine, Maimonides Medical Center, Brooklyn, NY, United States.
Comparative Effectiveness Outcomes Research, Department of Sociomedical Sciences, Columbia University Mailman School of Public Health, New York, NY, United States.
Front Med (Lausanne). 2021 Aug 12;8:669587. doi: 10.3389/fmed.2021.669587. eCollection 2021.
Checkpoint inhibitor immunotherapy or immuno-oncology (IO) treatment in refractory cervical cancer yielded an objective response rate (ORR) of 12% in tumors expressing the programmed cell death ligand-1 (PD-L1) in the KEYNOTE-158 phase II study. We hypothesized that the positive response might be associated with the level of PD-L1 expression and/or the tumor mutation burden (TMB). We also aimed to analyze if responses could be associated with platinum sensitivity. This is a retrospective study of all consecutive patients with cervical cancer who received pembrolizumab or nivolumab. Ten patients were identified. Median age was 64.5 years old (range 48-80). The response rate was 70% and the median duration of response was 21.0 months (range 1.8-26.7) after 20.7 months of follow-up (range 2.0-31.0). The response rate was 80% in patients with PD-L1 combined positive score (CPS) ≥ 10, and 75% in patients with tumor mutation burden (TMB) ≥ 10 mut/Mb. The mean progression-free survival (PFS) for the entire cohort was 20.2 months (95% CI 12.0-28.5). Seven patients had treatment for >12 months (range 14.6-31.0). Five patients were platinum-sensitive and 5 patients were platinum-resistant at the time of immunotherapy, and the response rate was similar regardless of platinum sensitivity. The positive response to IO treatment in advanced cervical cancer in this study was higher than published, and a possible association with the level of PD-L1 expression and the TMB level was suggested. A PD-L1 CPS score ≥ 10 or TMB ≥ 10 may be biomarkers to correlate with response, which should be explored in large studies.
在KEYNOTE-158 II期研究中，难治性宫颈癌的检查点抑制剂免疫疗法或免疫肿瘤学（IO）治疗在表达程序性细胞死亡配体-1（PD-L1）的肿瘤中的客观缓解率（ORR）为12%。我们假设阳性反应可能与PD-L1表达水平和/或肿瘤突变负荷（TMB）有关。我们还旨在分析反应是否与铂敏感性相关。这是一项对所有接受派姆单抗或纳武单抗治疗的连续性宫颈癌患者的回顾性研究。共确定了10名患者。中位年龄为64.5岁（范围48 - 80岁）。经过20.7个月的随访（范围2.0 - 31.0个月）后，缓解率为70%，中位缓解持续时间为21.0个月（范围1.8 - 26.7个月）。PD-L1联合阳性评分（CPS）≥10的患者缓解率为80%，肿瘤突变负荷（TMB）≥10 mut/Mb的患者缓解率为75%。整个队列的平均无进展生存期（PFS）为20.2个月（95%CI 12.0 - 28.5）。7名患者接受治疗超过12个月（范围14.6 - 31.0个月）。5名患者在免疫治疗时对铂敏感，5名患者对铂耐药，无论铂敏感性如何，缓解率相似。本研究中晚期宫颈癌对IO治疗的阳性反应高于已发表的结果，并提示可能与PD-L1表达水平和TMB水平有关。PD-L1 CPS评分≥10或TMB≥10可能是与反应相关的生物标志物，应在大型研究中进行探索。
