一线靶向治疗或 PD-1 为基础的免疫检查点抑制治疗后 LDH 升高的黑色素瘤患者的结局。
Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition.
机构信息
Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Department of Dermatology, University Hospital Tübingen, Tübingen, Germany.
出版信息
Eur J Cancer. 2021 May;148:61-75. doi: 10.1016/j.ejca.2021.01.034. Epub 2021 Mar 15.
BACKGROUND
Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking.
METHODS
This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting.
RESULTS
Among 173 BRAFV600-mutant patients, PFS at 12 months in the TT group was 22% compared with 52% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.6, 95% CI 0.4-1.0, p = 0.07) and 18% in the anti-PD-1 monotherapy group (HR 1.8, 95% CI 1.2-2.8, p = 0.003). Twelve months' OS was 48% in the TT group compared with 83% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.5, 95% CI 0.3-1.0, p = 0.03) and 50% in the anti-PD-1 monotherapy group (HR 1.2, 95% CI 0.8-2.0, p = 0.37). The ORR in the TT group was 63%, compared with 55% and 20% in the combined anti-PD-1 and anti-CTLA-4 and anti-PD-1 monotherapy group, respectively. Among 314 patients receiving ICI first-line, PFS at 12 months was 33% in the anti-PD-1 group versus 38% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.8, 95% CI 0.6-1.0; p = 0.07). OS at 12 months was 54% in the anti-PD-1 group versus 66% in the combined ICI group (HR 0.7, 95% CI 0.5-1.0; p = 0.03). The ORR was 30% in the anti-PD-1 monotherapy group and 43% in the combined anti-PD-1 and anti-CTLA-4 group. Results from multivariate analysis confirmed the absence of qualitative confounding.
CONCLUSIONS
Among BRAF-mutant patients with elevated LDH, combined anti-PD-1 and anti-CTLA-4 blockade seems to be associated with prolonged OS compared with first-line TT. Among patients receiving ICI as a first-line treatment, OS appears to be longer for the combination of anti-PD-1 and anti-CTLA-4 than for anti-PD-1 alone.
背景
乳酸脱氢酶（LDH）升高是转移性黑色素瘤患者预后不良的已知预测和预后因素。由于该领域缺乏前瞻性研究，因此尚不清楚一线靶向治疗（TT）或免疫检查点抑制（ICI）在 LDH 升高的黑色素瘤患者中更有益。
方法
本研究是一项在全球 25 个黑色素瘤中心进行的多中心回顾性队列研究，旨在分析 LDH 升高的黑色素瘤患者的无进展生存期（PFS）和总生存期（OS）。通过使用逆概率治疗加权来解决混杂因素的作用。
结果
在 173 例 BRAFV600 突变患者中，TT 组 12 个月时的 PFS 为 22%，而联合抗 PD-1 和抗 CTLA-4 组为 52%（HR 0.6，95%CI 0.4-1.0，p=0.07），抗 PD-1 单药组为 18%（HR 1.8，95%CI 1.2-2.8，p=0.003）。TT 组 12 个月的 OS 为 48%，而联合抗 PD-1 和抗 CTLA-4 组为 83%（HR 0.5，95%CI 0.3-1.0，p=0.03），抗 PD-1 单药组为 50%（HR 1.2，95%CI 0.8-2.0，p=0.37）。TT 组的客观缓解率（ORR）为 63%，而联合抗 PD-1 和抗 CTLA-4 以及抗 PD-1 单药组的 ORR 分别为 55%和 20%。在 314 例接受 ICI 一线治疗的患者中，抗 PD-1 组 12 个月时的 PFS 为 33%，而联合抗 PD-1 和抗 CTLA-4 组为 38%（HR 0.8，95%CI 0.6-1.0；p=0.07）。抗 PD-1 组 12 个月时的 OS 为 54%，而联合 ICI 组为 66%（HR 0.7，95%CI 0.5-1.0；p=0.03）。抗 PD-1 单药组的 ORR 为 30%，联合抗 PD-1 和抗 CTLA-4 组为 43%。多变量分析的结果证实了不存在定性混杂。
结论
在 LDH 升高的 BRAF 突变患者中，联合抗 PD-1 和抗 CTLA-4 阻断似乎与 TT 一线治疗相比，OS 延长相关。在接受 ICI 作为一线治疗的患者中，抗 PD-1 和抗 CTLA-4 联合治疗的 OS 似乎比单独使用抗 PD-1 更长。
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