获得性对 PD1 为基础的治疗在转移性黑色素瘤的耐药性的特征和管理。
The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.
机构信息
Melanoma Institute Australia, The University of Sydney, NSW, Australia; Instituto do Cancer do Estado de Sao Paulo, SP, Brazil.
Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands.
出版信息
Eur J Cancer. 2024 Jan;196:113441. doi: 10.1016/j.ejca.2023.113441. Epub 2023 Nov 20.
BACKGROUND
Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown.
METHODS
Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined. Demographics, disease characteristics and subsequent treatments were evaluated.
RESULTS
299 melanoma pts were identified, median age 64y, 44% BRAFV600m. 172 (58%) received PD1 alone, 114 (38%) PD1/CTLA4 and 13 (4%) PD1 and an investigational drug. 90 (30%) pts had CR, 209 (70%) PR. Median time to AR was 12.6 mo (95% CI, 11.3, 14.2). Most (N = 193, 65%) progressed in a single organ site, and in a solitary lesion (N = 151, 51%). The most frequent sites were lymph nodes (38%) and brain (25%). Management at AR included systemic therapy (ST, 45%), local therapy (LT) +ST (31%), LT alone (21%), or observation (3%). There was no statistical difference in PFS2 or OS based on management, however, PFS2 was numerically superior for pts treated with ST alone who progressed off PD1 therapy than those who progressed on PD1 (2-year PFS2 42% versus 25%, p = 0.249). mOS from AR was 38.0 months (95% CI, 29.5-NR); longer in single-site versus multi-site progression (2-year OS 70% vs 54%, p < 0·001).
CONCLUSIONS
Acquired resistance to PD1 therapy in melanoma is largely oligometastatic, and pts may have a favorable survival outcome following salvage treatment.
背景
抗 PD-1 治疗（PD1）无论是单独使用还是与抗 CTLA-4（CTLA4）联合使用，初始反应率都很高，然而，在治疗后 12 个月内，20%的完全缓解（CR）和 30%的部分缓解（PR）患者在 6 年内会出现疾病进展。这种获得性耐药（AR）的性质和最佳管理方法尚不清楚。
方法
对 16 个中心对 PD1 治疗有反应但随后进展的患者进行了检查。评估了患者的人口统计学、疾病特征和后续治疗情况。
结果
共确定了 299 名黑色素瘤患者，中位年龄 64 岁，44%的患者为 BRAFV600m 突变。172 名（58%）患者单独接受 PD1 治疗，114 名（38%）患者接受 PD1/CTLA4 联合治疗，13 名（4%）患者接受 PD1 和一种研究药物治疗。90 名（30%）患者达到 CR，209 名（70%）患者达到 PR。AR 的中位时间为 12.6 个月（95%CI，11.3，14.2）。大多数（N=193，65%）患者在单一器官部位进展，并且在单一病变部位进展（N=151，51%）。最常见的部位是淋巴结（38%）和脑（25%）。AR 管理包括系统治疗（ST，45%）、局部治疗（LT）+ST（31%）、LT 单独治疗（21%）或观察（3%）。基于管理方法，PFS2 或 OS 无统计学差异，但与 PD1 治疗进展的患者相比，单独接受 ST 治疗且 PD1 治疗进展的患者的 PFS2 更高（2 年 PFS2 为 42% vs 25%，p=0.249）。从 AR 开始的 mOS 为 38.0 个月（95%CI，29.5-NR）；单一部位进展比多部位进展的患者生存期更长（2 年 OS 为 70% vs 54%，p<0.001）。
结论
黑色素瘤患者对 PD1 治疗的获得性耐药主要为寡转移，挽救治疗后患者可能有较好的生存结果。
Zotero 插件