Wang Xuan, Ji Qing, Yan Xieqiao, Lian Bin, Si Lu, Chi Zhihong, Sheng Xinan, Kong Yan, Mao Lili, Bai Xue, Tang Bixia, Li Siming, Zhou Li, Cui Chuanliang, Guo Jun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Research Institute, Beijing, China.
Front Oncol. 2020 Sep 29;10:546604. doi: 10.3389/fonc.2020.546604. eCollection 2020.
Anti-programmed cell death protein 1 (PD-1) monoclonal antibody therapy is becoming a standard treatment for advanced melanoma that produces durable responses and prolonged survival, but the prognosis of patients with liver metastases is still unsatisfactory. Here, we analyzed five clinical studies (second-line or later, JS001-I-PK, CT4, KN151, BGB-A317-102, and SHR-1210-102; performed between 2015 and 2018) of anti-PD-1 monotherapy for advanced melanoma to explore prognostic variables for patients with liver metastases. A total of 168 patients with stage IV melanoma were included, among which 47 had liver metastasis and 121 did not. The objective response rate (ORR) of the no liver metastasis group was significantly higher than that of the liver metastasis group (20.7 vs. 4.3%, < 0.05). The median progression-free survival (PFS) time was 3.6 months for the patients with liver metastasis and 7.4 months for those without liver metastasis ( < 0.05). The no liver metastasis group also had a longer median overall survival (OS) time than the liver metastasis group (22.8 vs. 15.7 months, < 0.05). Multivariate analysis showed that liver metastasis was negatively associated with PFS. In the liver metastasis group, compared to metastases in other sites (lymph node, subcutaneous, and lung), liver metastases responded worse to anti-PD-1 monotherapy and were most likely to progress. Intrahepatic progression (defined as an increase in liver metastasis by more than 20% from baseline or having new liver metastases, < 0.05) was negatively associated with OS, which indicates the need to find a more effective therapy that can target liver metastases. Interestingly, with a median PFS and OS time of 6.0 and 30.9 months, respectively, previous oncolytic virotherapy might bring more benefits to patients with liver metastasis, but confirmation is needed because of the limited number of samples. These findings emphasize that liver metastasis is a poor prognostic factor for advanced melanoma treated with anti-PD-1 monotherapy. Further exploration is still needed to find a new treatment approach for these patients.
抗程序性细胞死亡蛋白1（PD-1）单克隆抗体疗法正成为晚期黑色素瘤的标准治疗方法，可产生持久反应并延长生存期，但肝转移患者的预后仍不尽人意。在此，我们分析了五项关于抗PD-1单药治疗晚期黑色素瘤的临床研究（二线或更晚期，JS001-I-PK、CT4、KN151、BGB-A317-102和SHR-1210-102；于2015年至2018年进行），以探索肝转移患者的预后变量。共纳入168例IV期黑色素瘤患者，其中47例有肝转移，121例无肝转移。无肝转移组的客观缓解率（ORR）显著高于肝转移组（20.7%对4.3%，<0.05）。肝转移患者的中位无进展生存期（PFS）为3.6个月，无肝转移患者为7.4个月（<0.05）。无肝转移组的中位总生存期（OS）也比肝转移组长（22.8个月对15.7个月，<0.05）。多变量分析显示肝转移与PFS呈负相关。在肝转移组中，与其他部位（淋巴结、皮下和肺）的转移相比，肝转移对抗PD-1单药治疗的反应更差，且最易进展。肝内进展（定义为肝转移较基线增加超过20%或出现新的肝转移，<0.05）与OS呈负相关，这表明需要找到一种更有效的靶向肝转移的治疗方法。有趣的是，既往溶瘤病毒疗法的中位PFS和OS时间分别为6.0个月和30.9个月，可能会给肝转移患者带来更多益处，但由于样本数量有限，尚需证实。这些发现强调肝转移是抗PD-1单药治疗晚期黑色素瘤的不良预后因素。仍需进一步探索为这些患者找到新的治疗方法。
