Miller Kathryn M, Filippova Olga T, Hayes Sara A, Abu-Rustum Nadeem R, Aghajanian Carol, Broach Vance, Ellenson Lora H, Selenica Pier, Jewell Elizabeth L, Kyi Chrisann, Lakhman Yuliya, Mueller Jennifer J, O'Cearbhaill Roisin E, Park Kay J, Sonoda Yukio, Zamarin Dmitriy, Weigelt Britta, Leitao Mario M, Friedman Claire F
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Gynecol Oncol Rep. 2021 Jul 10;37:100831. doi: 10.1016/j.gore.2021.100831. eCollection 2021 Aug.
Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab.
We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria.
The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03).
Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.
自帕博利珠单抗获批用于治疗晚期或复发性程序性死亡受体配体1（PD-L1）阳性（综合阳性评分[CPS]＞1%）宫颈癌以来，与疗效相关的临床特征仍不明确。我们试图描述在本机构接受帕博利珠单抗治疗并获得持久临床获益的晚期宫颈癌患者的临床病理特征。
我们对2017年8月至2019年11月接受帕博利珠单抗单药治疗的14例复发性或转移性宫颈癌患者进行了一项回顾性队列研究，并随访至2020年11月1日。回顾的临床数据包括年龄、组织学、肿瘤分子谱分析结果、诊断时的分期、治疗史、抗程序性死亡受体1（PD-1）治疗开始时转移性疾病的基线模式以及结局。采用实体瘤疗效评价标准（RECIST）v1.1版通过计算机断层扫描评估治疗反应。
客观缓解率为21%（n = 3），包括2例部分缓解和1例完全缓解。2例患者（14%）疾病稳定达6个月或更长时间，观察到的持久临床获益率为36%。按获得临床获益的患者分层时，仅在基线时转移至肺和/或淋巴结与对帕博利珠单抗的反应改善相关（n = 7，p = 0.02），并与无进展生存期（PFS）和总生存期（OS）显著改善相关。与无反应者相比，获得持久临床获益者的肿瘤突变负荷更高（中位数分别为12.7个与3.5个突变/百万碱基，p = 0.03）。
我们的研究结果突出了可能选择出最有可能从帕博利珠单抗单药治疗中获益人群的临床特征，并强调了识别其他反应生物标志物的必要性。
