Fox Chase Cancer Center, Philadelphia, PA, United States.
MD Anderson Cancer Center, Houston, TX, United States.
Br J Cancer. 2020 Apr;122(9):1309-1314. doi: 10.1038/s41416-020-0775-0. Epub 2020 Mar 10.
Metastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs.
Two open-label, phase 2 studies enrolled patients with G3NEN (Ki-67 > 20%) to receive Pembrolizumab at 200 mg I.V. every 3 weeks. Radiographic evaluation was conducted every 9 weeks with overall response rate as the primary endpoint.
Between November 2016 and May 2018, 29 patients (13 males/16 females) with G3NENs were enrolled. One patient (3.4%) had an objective response and an additional six patients (20.7%) had stable disease, resulting in a disease control rate of 24.1%. Disease control rate (DCR) at 18 weeks was 10.3% (3/29). There was no difference in the DCR, PFS or OS between the PD-L1-negative and -positive groups (p 0.56, 0.88 and 0.55, respectively). Pembrolizumab was well tolerated with only 9 grade 3, and no grade 4 events considered drug-related.
Pembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Successful completion of our trials suggest studies in G3NENs are feasible and present an unmet need. Further research to identify active combination therapies should be considered.
NCT02939651 (10/20/2016).
转移性高级别神经内分泌肿瘤（G3NEN）在铂类治疗进展后治疗选择有限。我们研究了派姆单抗在既往治疗转移性 G3NEN 患者中的作用。
两项开放标签、2 期研究招募了 Ki-67＞20%的 G3NEN 患者，接受 200mg 静脉注射派姆单抗，每 3 周 1 次。每 9 周进行一次影像学评估，主要终点为总缓解率。
2016 年 11 月至 2018 年 5 月期间，共纳入 29 例 G3NEN 患者（男 13 例，女 16 例）。1 例患者（3.4%）有客观缓解，另外 6 例患者（20.7%）疾病稳定，疾病控制率为 24.1%。18 周时疾病控制率（DCR）为 10.3%（29/29）。PD-L1 阴性和阳性组的 DCR、无进展生存期（PFS）或总生存期（OS）无差异（p 0.56、0.88 和 0.55）。派姆单抗耐受性良好，仅 9 例为 3 级，无 4 级药物相关事件。
派姆单抗可安全用于 G3NEN 患者，但作为单一药物活性有限。我们的试验成功完成表明，在 G3NEN 中开展研究是可行的，存在未满足的需求。应考虑进一步研究以确定有效的联合治疗方案。
NCT02939651（2016 年 10 月 20 日）。
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