Scholarlink

Background <p>Enfortumab vedotin plus pembrolizumab (EV/Pem) has improved the survival of patients with advanced urothelial carcinoma; however, many patients suffer treatment-related adverse events, particularly skin toxicity. This study aimed to clarify the clinical impact of skin-toxicity timing on treatment outcomes.</p> Methods <p>We retrospectively analyzed patients with advanced urothelial carcinoma treated with EV/Pem. Patients were categorized into three groups according to skin-toxicity timing: no rash, early-onset rash (&lt; 1 month), and late-onset rash (≥ 1 month). Baseline clinical and laboratory characteristics were compared among groups and incorporated into multivariable Cox proportional hazards analyses. Kaplan-Meier analyses with pairwise log-rank tests were performed to evaluate progression-free survival (PFS) and overall survival (OS). The 1-month cutoff was selected for clinical interpretability.</p> Results <p>The three-group analysis included 210 patients: no rash (<i>n</i> = 87), early-onset rash (<i>n</i> = 84), and late-onset rash (<i>n</i> = 39). Late-onset rash was associated with significantly prolonged PFS and OS in conventional analyses. In multivariable analysis, late-onset rash was significantly associated with prolonged PFS (HR 0.34, 95% CI 0.15–0.74, <i>p</i> = 0.007) and OS (HR 0.25, 95% CI 0.07–0.81, <i>p</i> = 0.02). Because late-onset rash could only be assigned after continued observation, these associations should be interpreted as exploratory and potentially affected by immortal time bias. In the 3-month landmark analysis, PFS remained significantly longer in the late-onset than early-onset rash group, whereas OS did not differ significantly.</p> Conclusions <p>Skin toxicity during EV/Pem therapy appears to have timing-dependent prognostic implications. Late-onset rash showed favorable outcomes in conventional analyses, but these findings should be considered hypothesis-generating.</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

Timing-dependent skin toxicity phenotypes during enfortumab vedotin plus pembrolizumab therapy for advanced urothelial carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月27日

查看全文
  • Mamoru Hashimoto,
  • Lan Inoki,
  • Yutaka Yamamoto,
  • Wataru Fukuokaya,
  • Takafumi Yanagisawa,
  • Keiichiro Mori,
  • Ryoichi Maenosono,
  • Yuki Yoshikawa,
  • Takuya Tsujino,
  • Masanobu Saruta,
  • Takuhisa Nukaya,
  • Yuya Oishi,
  • Keita Tamura,
  • Seitetsu Sugiyama,
  • Hirofumi Morinaka,
  • Kazumasa Komura,
  • Kiyoshi Takahara,
  • Teruo Inamoto,
  • Kazutoshi Fujita

摘要

Background

Enfortumab vedotin plus pembrolizumab (EV/Pem) has improved the survival of patients with advanced urothelial carcinoma; however, many patients suffer treatment-related adverse events, particularly skin toxicity. This study aimed to clarify the clinical impact of skin-toxicity timing on treatment outcomes.

Methods

We retrospectively analyzed patients with advanced urothelial carcinoma treated with EV/Pem. Patients were categorized into three groups according to skin-toxicity timing: no rash, early-onset rash (< 1 month), and late-onset rash (≥ 1 month). Baseline clinical and laboratory characteristics were compared among groups and incorporated into multivariable Cox proportional hazards analyses. Kaplan-Meier analyses with pairwise log-rank tests were performed to evaluate progression-free survival (PFS) and overall survival (OS). The 1-month cutoff was selected for clinical interpretability.

Results

The three-group analysis included 210 patients: no rash (n = 87), early-onset rash (n = 84), and late-onset rash (n = 39). Late-onset rash was associated with significantly prolonged PFS and OS in conventional analyses. In multivariable analysis, late-onset rash was significantly associated with prolonged PFS (HR 0.34, 95% CI 0.15–0.74, p = 0.007) and OS (HR 0.25, 95% CI 0.07–0.81, p = 0.02). Because late-onset rash could only be assigned after continued observation, these associations should be interpreted as exploratory and potentially affected by immortal time bias. In the 3-month landmark analysis, PFS remained significantly longer in the late-onset than early-onset rash group, whereas OS did not differ significantly.

Conclusions

Skin toxicity during EV/Pem therapy appears to have timing-dependent prognostic implications. Late-onset rash showed favorable outcomes in conventional analyses, but these findings should be considered hypothesis-generating.