Department of Medical Oncology, Teaching Hospital Cochin, AP-HP, University Paris Descartes, 123 Bd Port Royal, 75 679, Paris Cedex 14, France.
Medical Oncology, Paris Descartes University, Bat Copernic, 5ème, 123 Bd Port Royal, 75 679, Paris Cedex 14, France.
Invest New Drugs. 2017 Dec;35(6):842-847. doi: 10.1007/s10637-017-0476-6. Epub 2017 May 31.
Background The identification of the melanoma patients sensitive to anti-PD-1 inhibitors, nivolumab or pembrolizumab, is a major therapeutic challenge and an urgent need. We hypothesized that the natural history of the disease might partly reflect the immune state of the patients. Methods We analyzed our cohort of melanoma patients treated with anti-PD-1 from August 2014 to January 2016 in our institution. Objective response was defined as a complete or partial response according to v1.1 RECIST criteria. Results Among 63 metastatic melanoma patients, the overall response rate was 43%. Median time from diagnosis to anti-PD-1 initiation was longer among responders than non-responders (64 months vs. 35 months, p = 0.02). The response rate was 10% in patients starting anti-PD-1 within 1 year, 35% after 1 to 5 years and 63% after 5 years. Performance status (PS) 0 was also associated with enhanced tumor response: 70% of responders were PS 0 vs. 36% of non-responders (p = 0.04). PS 0, normal LDH levels and wild-type BRAF status were significant predictors of progression free survival. Conclusion A long time lapse from diagnosis to anti-PD-1 initiation and PS 0 are associated with higher sensitivity to anti-PD-1 in melanoma patients. These two clinical features might reflect a potentially intact immune system of the host.
背景 鉴定对抗 PD-1 抑制剂（如 nivolumab 或 pembrolizumab）敏感的黑色素瘤患者是一项重大的治疗挑战和迫切需求。我们假设疾病的自然病程在一定程度上反映了患者的免疫状态。
方法 我们分析了我院 2014 年 8 月至 2016 年 1 月期间接受抗 PD-1 治疗的黑色素瘤患者队列。客观缓解定义为根据 v1.1 RECIST 标准完全或部分缓解。
结果 在 63 例转移性黑色素瘤患者中，总体缓解率为 43%。与无应答者相比，应答者从诊断到开始抗 PD-1 的中位时间更长（64 个月 vs. 35 个月，p=0.02）。在开始抗 PD-1 治疗的 1 年内，应答率为 10%，1-5 年为 35%，5 年后为 63%。表现状态（PS）0 也与增强的肿瘤反应相关：70%的应答者 PS 0，而非应答者为 36%（p=0.04）。PS 0、正常 LDH 水平和野生型 BRAF 状态是无进展生存期的显著预测因素。
结论 从诊断到开始抗 PD-1 治疗的时间较长和 PS 0 与黑色素瘤患者对抗 PD-1 的敏感性增加相关。这两个临床特征可能反映了宿主潜在完整的免疫系统。
