Jindal Tanya, Jiang Cindy, Alhalabi Omar, Nizam Amanda, Nguyen Charles, Talukder Rafee, Bakaloudi Dimitra, Davidsohn Matthew, Freeman Dory, Glover Michael, Khaki Ali Raza, Evans Sean, Lemke Emily, Bose Rohit, Sim Woogwang, Pywell Cameron, Basu Arnab, Kilari Deepak, Barata Pedro C, Bilen Mehmet A, Zakharia Yousef, Milowsky Matthew I, Shah Sumit A, Bellmunt Joaquim, Grivas Petros, Emamekhoo Hamid, Davis Nancy B, Gupta Shilpa, Hoimes Christopher, Campbell Matthew T, Alva Ajjai, Koshkin Vadim S
Helen Diller Family Cancer Center, University of California-San Francisco, San Francisco, CA, USA.
MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Eur Urol Oncol. 2025 Apr;8(2):258-262. doi: 10.1016/j.euo.2024.12.006. Epub 2024 Dec 20.
Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.
恩杂鲁胺（EV）在晚期尿路上皮癌（aUC）中用作单药治疗或与帕博利珠单抗联合使用，但与EV疗效相关的生物标志物数据有限。我们在UNITE研究中确定了170例接受EV单药治疗且有分子生物标志物数据的患者。使用逻辑回归（未调整）比较有或没有特定生物标志物的组的客观缓解率（ORR），并使用对数秩检验和Cox比例风险模型（CPHM）比较从开始使用EV起的无进展生存期（PFS）和总生存期（OS）。还使用考虑临床特征的CPHM在单独的多变量分析中评估分子生物标志物。患者中位年龄为70岁；队列中78%为男性，65%为纯UC组织学类型。CDKN2A改变的患者中位PFS较短（4.6个月对6个月；p = 0.024），CDKN2B改变的患者中位PFS也较短（4.4个月对6个月；p = 0.008）。肿瘤突变负荷高的患者中位OS较长（13.6个月对8.3个月；p = 0.014）。TSC1改变的患者ORR较高（87%对51%；p = 0.018）。在多变量分析中，CDKN2A和CDKN2B改变与中位PFS较差相关。这项对aUC患者的多机构回顾性研究确定了与EV单药治疗疗效相关的潜在生物标志物，应进一步研究。患者总结：我们研究了尿路肿瘤的基因变化，这些变化可能与晚期疾病患者对恩杂鲁胺（EV）治疗的反应有关。与突变较少的肿瘤相比，突变数量较多的肿瘤在EV治疗后的生存期更长。然而，两个基因（CDKN2A和CDKN2B）的突变与EV治疗后的较差结果相关。这些发现不会影响当前的临床实践，但应在未来的研究中进一步调查。
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