Ngoi N Y L, Heong V, Lee X W, Huang Y Q, Thian Y L, Choo B A, Lim D, Lim Y W, Lim S E, Ilancheran A, Soong R, Tan D S P
Department of Hematology-Oncology, National University Cancer Institute, Singapore, 5 Lower Kent Ridge Rd, Singapore 119074, Republic of Singapore.
Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599, Republic of Singapore.
Gynecol Oncol Rep. 2018 Jan 31;24:1-5. doi: 10.1016/j.gore.2018.01.009. eCollection 2018 May.
Optimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in (R612W), (E542K) and (E365K). In 2 patients, despite progressive disease defined by RECIST v1.1, symptom stabilization on pembrolizumab was observed. The tumors of both patients had PD-1 expression in ≥1% of stromal lymphocytes. All patients with response or clinical benefit had CPS for PD-L1 ≥ 1. NGS revealed mutations in 3 tumors. Pembrolizumab is a promising therapeutic option in advanced cervical cancer. Further evaluation of biomarkers may guide optimal patient selection.
一线化疗后晚期宫颈癌的最佳治疗方案仍不明确。程序性细胞死亡蛋白1（PD-1）抑制剂帕博利珠单抗的免疫检查点抑制作用正在研究中。我们分析了4例接受二线帕博利珠单抗治疗的转移性宫颈癌患者肿瘤的微环境和分子遗传特征，以确定预测性生物标志物。所有患者均接受2mg/kg帕博利珠单抗治疗，每3周一次，直至疾病进展。对肿瘤样本进行了PD-1、PD-L1、CD3和CD8的免疫组织化学（IHC）检测，以及50个癌症相关基因的二代测序（NGS）。所有患者对治疗耐受性良好，无因毒性而停药的情况。1例患者出现显著且持久的部分缓解，在报告本系列时，接受帕博利珠单抗治疗病情仍稳定，无进展生存期（PFS）为21个月。3例患者疾病进展为最佳反应。在这位特殊的反应者中，肿瘤无PD-L1表达，然而，PD-L1的联合阳性评分（CPS）为1，我们在（R612W）、（E542K）和（E365K）中发现了体细胞突变。在2例患者中，尽管根据RECIST v1.1标准确定为疾病进展，但观察到帕博利珠单抗治疗后症状稳定。两位患者的肿瘤在≥1%的基质淋巴细胞中均有PD-1表达。所有有反应或临床获益的患者PD-L1的CPS≥1。NGS在3个肿瘤中发现了突变。帕博利珠单抗是晚期宫颈癌一种有前景的治疗选择。对生物标志物的进一步评估可能会指导最佳患者选择。
