Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib
Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib
复制标题
DOI：
10.1016/j.annonc.2019.10.002
复制
发表时间：
2020-01-01
影响因子：
50.5
通讯作者：
Schadendorf, D.
中科院分区：
文献类型：
--
作者：
Ascierto, P. A.;Lewis, K. D.;Schadendorf, D.
背景：我们进行了一项回顾性探索性分析，以评估基线肿瘤免疫浸润对完全切除的 IIC-IIIC 期黑色素瘤患者在 BRIM8 研究中接受辅助维莫非尼单药治疗或安慰剂的无病生存 (DFS) 结果的影响。 患者和方法：BRIM8 是一项 III 期、国际、双盲、随机、安慰剂对照研究。符合条件的 BRAF(V600) 突变阳性、完全切除的黑色素瘤患者被随机分配接受口服维莫非尼（960 毫克，每天两次）或匹配的安慰剂治疗，为期 52 周。主要终点是 DFS。回顾性探讨了通过免疫组织化学测量的 CD8+ T 细胞浸润和程序性死亡配体 1 (PD-L1) 表达与 DFS 的关系。 结果：498 名患者被随机分配接受辅助维莫非尼 (n = 250) 或安慰剂 (n = 248)；大约 60% 的患者的肿瘤样本可用于生物标志物分析。在汇集的生物标志物群体中，安慰剂治疗的患者 CD8+ T 细胞 = 1%（7.7 个月与 47.8 个月）。与安慰剂相比，CD8+ T 细胞 = 1% 的患者的 DFS 获益更大（HR 0.77；95% CI 0.48-1.22）。同样，肿瘤中 PD-L1+ 免疫细胞 (IC) = 5% 的安慰剂治疗患者的中位 DFS 较短（7.2 个月与 47.8 个月）。在 PD-L1+IC = 5% 的患者中观察到维罗非尼与安慰剂相比具有更大的 DFS 益处（HR 0.99；95% CI 0.58-1.69）。结论：CD8+ T 细胞和 PD-L1+IC 的存在是 DFS 的有利预后因素。维莫非尼辅助治疗可以克服与低 CD8+ T 细胞计数或 PD-L1 表达相关的不良 DFS 预后。
Background: We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC-IIIC melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study.Patients and methods: BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAF(V600) mutation-positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively.Results: Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with = 1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with = 1% CD8+ T cells (HR 0.77; 95% CI 0.48-1.22). Likewise, median DFS was shorter among placebo-treated patients with = 5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with = 5% PD-L1+IC (HR 0.99; 95% CI 0.58-1.69).Conclusions: The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression.