Clinical Oncology Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Cracow, Poland.
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Adv Med Sci. 2020 Sep;65(2):316-323. doi: 10.1016/j.advms.2020.05.005. Epub 2020 Jun 15.
Immunotherapy has become a standard treatment option for patients with metastatic melanoma, and the use of checkpoint inhibitors significantly improves the treatment outcomes in this group.
A total of 116 patients with metastatic melanoma were enrolled in the study. In the first line, they were treated with an anti-PD-1 inhibitor (nivolumab or pembrolizumab), following which ipilimumab was used as the second-line therapy.
BRAF mutation was detected in 12 patients (10%). The median progression-free survival (PFS) of ipilimumab treatment was 2.8 months, the overall survival (OS) was 5.1 months. The rate of 6-month survival was 45%, 1-year survival was 24%, and 2-year survival was 3%. The responses to treatment were: complete response in 2 cases (2%), partial response in 7 cases (6%), stable disease in 39 cases (34%). In multivariate analysis, normal levels of lactate dehydrogenase (LDH) were associated with a longer median OS and PFS (p = 0.02 and p = 0.009, respectively), while 2 or less number of metastatic locations and the presence of BRAF mutations were correlated with a longer OS (p = 0.041 and p = 0.024, respectively).
Ipilimumab could be considered after anti-PD-1 treatment. Treatment with ipilimumab following anti-PD-1 therapy showed beneficial effects in patients with normal levels of LDH, 2 or less number of metastatic locations, and BRAF-mutated melanoma. However, further studies are required to confirm our results as the study included a low number of patients with BRAF mutation-positive melanoma. No significant increase in toxicity was detected with the use of ipilimumab after anti-PD-1 therapy.
免疫疗法已成为转移性黑色素瘤患者的标准治疗选择，而检查点抑制剂的使用显著改善了这一群体的治疗效果。
共有 116 名转移性黑色素瘤患者入组本研究。一线治疗采用抗 PD-1 抑制剂（nivolumab 或 pembrolizumab），随后二线治疗采用 ipilimumab。
检测到 12 例（10%）患者存在 BRAF 突变。Ipilimumab 治疗的中位无进展生存期（PFS）为 2.8 个月，总生存期（OS）为 5.1 个月。6 个月生存率为 45%，1 年生存率为 24%，2 年生存率为 3%。治疗反应为：完全缓解 2 例（2%），部分缓解 7 例（6%），稳定疾病 39 例（34%）。多变量分析显示，乳酸脱氢酶（LDH）正常水平与较长的中位 OS 和 PFS 相关（p=0.02 和 p=0.009），而 2 个或更少的转移部位和存在 BRAF 突变与较长的 OS 相关（p=0.041 和 p=0.024）。
Ipilimumab 可在抗 PD-1 治疗后考虑使用。在 LDH 正常水平、转移部位 2 个或更少、存在 BRAF 突变的黑色素瘤患者中，抗 PD-1 治疗后使用 ipilimumab 治疗显示出有益效果。然而，由于本研究纳入的 BRAF 突变阳性黑色素瘤患者数量较少，需要进一步研究来证实我们的结果。抗 PD-1 治疗后使用 ipilimumab 未检测到毒性显著增加。
