Scholarlink

Background <p>Acral melanoma (AM) and mucosal melanoma (MM) respond poorly to anti-PD-1 monotherapy. Therefore, there is an urgent need to explore safe and effective anti-PD-1-based combined therapies.</p> Methods <p>A nationwide real-world cohort study consecutively included patients with advanced melanoma treated with anti-PD-1 in China between July 1, 2018, and June 30, 2023. The&#xa0;Research Electronic Data Capture<b> (</b>REDCap) system was used across all centers. The primary endpoints were progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs), with a secondary endpoints of objective response rate (ORR). Multivariable Cox and logistic regression models were conducted to compare the efficacy and safety of different anti-PD-1-based combination therapies with anti-PD-1 monotherapy. Stratified analyses were performed to evaluate the effect of therapies in cutaneous, acral, mucosal, and unknown primary subtypes.</p> Results <p>A total of 431 advanced melanoma patients comprising 22% cutaneous, 39% acral, 32% mucosal, and 7% unknown primary subtypes were included. Multivariable Cox analysis indicated that compared with anti-PD-1 monotherapy, anti-PD-1 + anti-VEGF + chemotherapy (HR, 0.4 [0.2, 0.7], <i>P</i> = 0.005) and anti-PD-1 + anti-VEGF therapy (HR, 0.4 [0.2, 0.9], <i>P</i> = 0.018) showed significant PFS benefit in AM and MM, respectively. Notably, anti-PD-1 + IFN-α1b showed a nonsignificantly longer PFS and OS in AM. A multivariate logistic regression model found that anti-PD-1-based combination therapies were significantly associated with grade 1–2 irAEs, while only anti-PD-1 + IFN-α1b + anti-VEGF therapy was significantly associated with high risk of grade 3–5 irAEs (OR, 4.4 [1.3–14.7], <i>p</i> = 0.017), without a significant survival benefit.</p> Conclusions <p>Our results provide evidence for anti-PD-1 + anti-VEGF + chemotherapy and anti-PD-1 + IFN-α1b in AM and anti-PD-1 + anti-VEGF therapy in MM, as the long-term benefit and acceptable toxicity. However, for the patients who received anti-PD-1 + IFN-α1b + anti-VEGF, cautionary notes and awareness of drug safety should be raised, as the triple therapy with multiple mechanisms may increase the potential risk of toxicity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Efficacy and safety of anti-PD-1-based therapies in advanced melanoma across acral and mucosal subtypes: a nationwide retrospective cohort study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月23日

查看全文
  • Yuan Qiao,
  • Xiao Fu,
  • Iltaf Hussain,
  • Weihong Ge,
  • Wei Yang,
  • Renbin Jiang,
  • Xiaoyan Dai,
  • Haisheng Chen,
  • Jinyi Zhao,
  • Meng Tang,
  • Fei Mu,
  • Hao Wang,
  • Qiuhui Wu,
  • Xing Xia,
  • Yunnan Zhang,
  • Suzhi Ji,
  • Ying Xu,
  • Xinrui Cao,
  • Jiexin Wang,
  • Le Gao,
  • Jingwen Wang,
  • Yu Yao,
  • Yu Fang

摘要

Background

Acral melanoma (AM) and mucosal melanoma (MM) respond poorly to anti-PD-1 monotherapy. Therefore, there is an urgent need to explore safe and effective anti-PD-1-based combined therapies.

Methods

A nationwide real-world cohort study consecutively included patients with advanced melanoma treated with anti-PD-1 in China between July 1, 2018, and June 30, 2023. The Research Electronic Data Capture (REDCap) system was used across all centers. The primary endpoints were progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs), with a secondary endpoints of objective response rate (ORR). Multivariable Cox and logistic regression models were conducted to compare the efficacy and safety of different anti-PD-1-based combination therapies with anti-PD-1 monotherapy. Stratified analyses were performed to evaluate the effect of therapies in cutaneous, acral, mucosal, and unknown primary subtypes.

Results

A total of 431 advanced melanoma patients comprising 22% cutaneous, 39% acral, 32% mucosal, and 7% unknown primary subtypes were included. Multivariable Cox analysis indicated that compared with anti-PD-1 monotherapy, anti-PD-1 + anti-VEGF + chemotherapy (HR, 0.4 [0.2, 0.7], P = 0.005) and anti-PD-1 + anti-VEGF therapy (HR, 0.4 [0.2, 0.9], P = 0.018) showed significant PFS benefit in AM and MM, respectively. Notably, anti-PD-1 + IFN-α1b showed a nonsignificantly longer PFS and OS in AM. A multivariate logistic regression model found that anti-PD-1-based combination therapies were significantly associated with grade 1–2 irAEs, while only anti-PD-1 + IFN-α1b + anti-VEGF therapy was significantly associated with high risk of grade 3–5 irAEs (OR, 4.4 [1.3–14.7], p = 0.017), without a significant survival benefit.

Conclusions

Our results provide evidence for anti-PD-1 + anti-VEGF + chemotherapy and anti-PD-1 + IFN-α1b in AM and anti-PD-1 + anti-VEGF therapy in MM, as the long-term benefit and acceptable toxicity. However, for the patients who received anti-PD-1 + IFN-α1b + anti-VEGF, cautionary notes and awareness of drug safety should be raised, as the triple therapy with multiple mechanisms may increase the potential risk of toxicity.