Zhaopei Liu, Kaifeng Jin, Ziyue Xu, Han Zeng, Xiaohe Su, Jingtong Xu, Yawei Ding, Hailong Liu, Yu Zhu, Le Xu, Jiejie Xu, Zewei Wang, Yuan Chang
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Our analysis encompassed the assessment of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of treatment-related adverse events (TrAEs).</p><p><strong>Results: </strong>In the general population, the median follow-up time was 12.1 months, and the median OS was not reached with a 12-month OS rate of 86.7%. The median PFS was 12.2 months (95% confidence interval [CI]: 6.6-17.7 months), with an ORR of 42.3% (95% CI: 23.4%-63.1%) and a DCR of 73.1% (95% CI: 55.2%-88.4%). Higher HER-2 expression is correlated with prolonged clinical benefit from DV (Log-rank P = 0.082. HER-2 IHC 2+ & 3 + vs. IHC 1+: Median PFS: 13.1 vs. 4.6 months; Response rate: 60.0% vs. 0.0%). History of durable response to platinum-based chemotherapy can also imply longer PFS and better response rate (Log-rank P = 0.086. Median PFS: 14.2 vs. 3.6 months. Response rate: 50.0% vs. 10.0%). Moreover, higher mutation burden (TMB) is closely related to better outcomes from DV therapy (Log-rank P = 0.011. Median PFS: 12.8 vs. 4.6 months. Response rate: 71.4% vs. 11.1%. Firth's penalized multivariable Cox regression: P = 0.015. Hazard Ratio: 0.165. 95% CI: 0.026-0.717).</p><p><strong>Conclusion: </strong>In conclusion, patients with higher HER-2 expression, positive responses to chemotherapy, or elevated TMB are more likely to benefit from DV. These discoveries support the rationale for employing HER-2 antibody-drug conjugates (ADCs) for mUC patients.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1432"},"PeriodicalIF":3.4000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465952/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinicopathological and molecular correlates of clinical benefit from disitamab vedotin (RC48), a HER-2-targeting antibody-drug conjugate, in metastatic urothelial carcinoma: a multi-center, real-world study.\",\"authors\":\"Zhaopei Liu, Kaifeng Jin, Ziyue Xu, Han Zeng, Xiaohe Su, Jingtong Xu, Yawei Ding, Hailong Liu, Yu Zhu, Le Xu, Jiejie Xu, Zewei Wang, Yuan Chang\",\"doi\":\"10.1186/s12885-025-14870-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Disitamab Vedotin (DV), a HER-2-targeting antibody-drug conjugate, has exhibited substantial clinical advantages in individuals with metastatic urothelial carcinoma (mUC). Nonetheless, the extent of therapeutic efficacy in real-world scenarios for mUC patients and the specific patient profiles with the most benefit from DV remain unclear.</p><p><strong>Methods: </strong>In this multi-center, retrospective, observational study, a total of 30 patients with mUC were included between April 2021 and March 2024 from three distinct hospitals, along with clinicopathological features and targeted sequencing data. Our analysis encompassed the assessment of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of treatment-related adverse events (TrAEs).</p><p><strong>Results: </strong>In the general population, the median follow-up time was 12.1 months, and the median OS was not reached with a 12-month OS rate of 86.7%. The median PFS was 12.2 months (95% confidence interval [CI]: 6.6-17.7 months), with an ORR of 42.3% (95% CI: 23.4%-63.1%) and a DCR of 73.1% (95% CI: 55.2%-88.4%). Higher HER-2 expression is correlated with prolonged clinical benefit from DV (Log-rank P = 0.082. HER-2 IHC 2+ & 3 + vs. IHC 1+: Median PFS: 13.1 vs. 4.6 months; Response rate: 60.0% vs. 0.0%). History of durable response to platinum-based chemotherapy can also imply longer PFS and better response rate (Log-rank P = 0.086. Median PFS: 14.2 vs. 3.6 months. Response rate: 50.0% vs. 10.0%). Moreover, higher mutation burden (TMB) is closely related to better outcomes from DV therapy (Log-rank P = 0.011. Median PFS: 12.8 vs. 4.6 months. Response rate: 71.4% vs. 11.1%. Firth's penalized multivariable Cox regression: P = 0.015. Hazard Ratio: 0.165. 95% CI: 0.026-0.717).</p><p><strong>Conclusion: </strong>In conclusion, patients with higher HER-2 expression, positive responses to chemotherapy, or elevated TMB are more likely to benefit from DV. 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引用次数: 0
摘要
diitamab Vedotin （DV）是一种her -2靶向抗体-药物偶联物，在转移性尿路上皮癌（mUC）患者中显示出实质性的临床优势。尽管如此，mUC患者在现实情况下的治疗效果程度以及从DV中获益最多的特定患者概况仍不清楚。方法：在这项多中心、回顾性、观察性研究中，共纳入了2021年4月至2024年3月来自三家不同医院的30例mUC患者，并提供了临床病理特征和靶向测序数据。我们的分析包括评估客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件（TrAEs）的发生率。结果：在一般人群中，中位随访时间为12.1个月，中位OS未达到，12个月OS率为86.7%。中位PFS为12.2个月（95%可信区间[CI]: 6.6-17.7个月），ORR为42.3% (95% CI: 23.4%-63.1%)， DCR为73.1% （95% CI: 55.2%-88.4%）。HER-2的高表达与DV的临床获益延长相关（Log-rank P = 0.082）。HER-2 IHC 2+ & 3 + vs。IHC 1+：中位PFS: 13.1 vs 4.6个月；应答率：60.0% vs. 0.0%)。对铂类化疗的持续反应史也意味着更长的PFS和更好的缓解率（Log-rank P = 0.086）。中位PFS: 14.2 vs. 3.6个月。回应率：50.0%对10.0%)。此外，更高的突变负担（TMB）与更好的DV治疗结果密切相关（Log-rank P = 0.011）。中位PFS: 12.8 vs 4.6个月。回应率：71.4% vs. 11.1%。费斯校正多变量Cox回归：P = 0.015。风险比：0.165。95% ci: 0.026-0.717)。结论：总之，HER-2表达较高、化疗反应阳性或TMB升高的患者更有可能从DV中获益。这些发现支持了使用HER-2抗体-药物偶联物（adc）治疗mUC患者的基本原理。
Clinicopathological and molecular correlates of clinical benefit from disitamab vedotin (RC48), a HER-2-targeting antibody-drug conjugate, in metastatic urothelial carcinoma: a multi-center, real-world study.
Introduction: Disitamab Vedotin (DV), a HER-2-targeting antibody-drug conjugate, has exhibited substantial clinical advantages in individuals with metastatic urothelial carcinoma (mUC). Nonetheless, the extent of therapeutic efficacy in real-world scenarios for mUC patients and the specific patient profiles with the most benefit from DV remain unclear.
Methods: In this multi-center, retrospective, observational study, a total of 30 patients with mUC were included between April 2021 and March 2024 from three distinct hospitals, along with clinicopathological features and targeted sequencing data. Our analysis encompassed the assessment of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of treatment-related adverse events (TrAEs).
Results: In the general population, the median follow-up time was 12.1 months, and the median OS was not reached with a 12-month OS rate of 86.7%. The median PFS was 12.2 months (95% confidence interval [CI]: 6.6-17.7 months), with an ORR of 42.3% (95% CI: 23.4%-63.1%) and a DCR of 73.1% (95% CI: 55.2%-88.4%). Higher HER-2 expression is correlated with prolonged clinical benefit from DV (Log-rank P = 0.082. HER-2 IHC 2+ & 3 + vs. IHC 1+: Median PFS: 13.1 vs. 4.6 months; Response rate: 60.0% vs. 0.0%). History of durable response to platinum-based chemotherapy can also imply longer PFS and better response rate (Log-rank P = 0.086. Median PFS: 14.2 vs. 3.6 months. Response rate: 50.0% vs. 10.0%). Moreover, higher mutation burden (TMB) is closely related to better outcomes from DV therapy (Log-rank P = 0.011. Median PFS: 12.8 vs. 4.6 months. Response rate: 71.4% vs. 11.1%. Firth's penalized multivariable Cox regression: P = 0.015. Hazard Ratio: 0.165. 95% CI: 0.026-0.717).
Conclusion: In conclusion, patients with higher HER-2 expression, positive responses to chemotherapy, or elevated TMB are more likely to benefit from DV. These discoveries support the rationale for employing HER-2 antibody-drug conjugates (ADCs) for mUC patients.
期刊介绍：
BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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