抗 PD-1 单药或联合抗 CTLA-4 治疗伴肝转移的晚期黑色素瘤患者。

Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases.

机构信息

Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, NSW, Australia; Crown Princess Mary Cancer Centre Westmead, Blacktown Hospital, Sydney, Australia.

Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia.

出版信息

Eur J Cancer. 2024 Jul;205:114101. doi: 10.1016/j.ejca.2024.114101. Epub 2024 May 7.

DOI:10.1016/j.ejca.2024.114101

PMID:38735161

Abstract

BACKGROUND

The combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases.

METHODS

We have conducted an international multicentre retrospective study. Patients with advanced melanoma with liver metastases treated with 1st line anti-PD1 monotherapy or with anti-CTLA-4 were included. The endpoints of this study were: objective response rate, progression-free survival and overall survival.

RESULTS

With a median follow-up from commencement of anti-PD-1 monotherapy or in combination with anti-CTLA-4 of 47 months (95% CI, 42-51), objective response rate was higher with combination therapy (47%) versus anti-PD-1 monotherapy (35%) (p = 0.0027), while progression-free survival and overall survival were not statistically different between both treatment groups. However, on multivariable analysis with multiple imputation for missing values and adjusting for predefined variables, combination of anti-PD1 and anti-CTLA-4 was associated with higher objective response (OR 2.21, 1.46 - 3.36; p < 0.001), progression-free survival (HR 0.73, 0.57 - 0.92; p = 0.009) and overall survival (HR 0.71, 0.54 - 0.94; p = 0.018) compared to anti-PD1 monotherapy.

CONCLUSIONS

Findings from this study will help guide treatment selection for patients who present with liver metastases, suggesting that combination therapy should be considered for this group of patients.

摘要

背景

与未经选择的晚期黑色素瘤患者的抗 PD-1 单药治疗相比，抗 PD-1 和抗 CTLA-4 的联合治疗与反应和生存的改善相关。肝转移患者是否也能从抗 PD-1 和抗 CTLA-4 的联合治疗中获益，尚不清楚。在这项研究中，我们试图评估与抗 PD-1 单药治疗相比，抗 PD-1 和抗 CTLA-4 的联合治疗是否能为肝转移患者带来更好的反应、无进展生存期和总生存期。

方法

我们进行了一项国际多中心回顾性研究。纳入了接受一线抗 PD1 单药治疗或抗 CTLA-4 治疗的晚期黑色素瘤伴肝转移患者。本研究的终点是：客观缓解率、无进展生存期和总生存期。

结果

自抗 PD-1 单药治疗或联合抗 CTLA-4 开始的中位随访时间为 47 个月（95%CI，42-51），联合治疗的客观缓解率（47%）高于抗 PD-1 单药治疗（35%）（p=0.0027），但两组的无进展生存期和总生存期无统计学差异。然而，在缺失值进行多重插补并调整了预设变量的多变量分析中，抗 PD1 和抗 CTLA-4 的联合治疗与更高的客观缓解率（OR 2.21，1.46-3.36；p<0.001）、无进展生存期（HR 0.73，0.57-0.92；p=0.009）和总生存期（HR 0.71，0.54-0.94；p=0.018）相关。