Barts Cancer Institute, Queen Mary University of London ECMC, Barts Health, London, UK.
Roche/Genentech, South San Francisco, CA, USA.
Eur Urol. 2024 Feb;85(2):114-122. doi: 10.1016/j.eururo.2023.06.007. Epub 2023 Jul 26.
Interim results from IMvigor010 showed an overall survival (OS) benefit for adjuvant atezolizumab (anti-PD-L1) versus observation in patients with circulating tumor DNA (ctDNA)-positive muscle-invasive urothelial carcinoma (MIUC).
To report updated OS and safety by ctDNA status.
DESIGN, SETTING, AND PARTICIPANTS: This ad hoc analysis from a global, open-label, randomized, phase 3 trial (NCT02450331) included intention-to-treat (ITT) population with evaluable cycle 1 day 1 (C1D1) ctDNA samples.
Atezolizumab (1200 mg every 3 wk) or observation for ≤1 yr.
OS, relapse rates, and safety by ctDNA status were assessed.
Among 581 of 809 ITT patients included, 214 (37%) were ctDNA positive. Atezolizumab did not improve OS versus observation in ITT patients (hazard ratio [HR] 0.91 [95% confidence interval {CI} 0.73-1.13]; median follow-up 46.8 mo [interquartile range, 36.1-53.6]). In the observation arm, ctDNA positivity versus negativity was associated with shorter OS (HR 6.3 [95% CI 4.3-9.3]). The ctDNA positivity identified patients with an OS benefit favoring atezolizumab versus observation (HR 0.59 [95% CI 0.42-0.83]). A greater reduction in ctDNA levels with atezolizumab (C3D1) was associated with longer OS (100% clearance, 60.0 mo [95% CI 35.5-not estimable]; 50-99% reduction, 34.3 mo [95% CI 15.2-not estimable]; <50% reduction, 19.9 mo [95% CI 16.4-32.2]). The ctDNA positivity at C1D1 + C3D1 was associated with relapse with greater sensitivity than C1D1 alone (68% vs 57%). Adverse events were more frequent with atezolizumab than with observation, regardless of ctDNA status. A study limitation was its exploratory design.
Evidence suggests that ctDNA positivity in MIUC predicts a benefit with atezolizumab. An in-progress prospective study will further evaluate these findings.
Among patients with urothelial cancer after surgery, survival was poorer if tumor-derived DNA was detected in their bloodstream; these patients' survival was longer with atezolizumab versus observation. Bloodstream tumor-derived DNA may identify patients who benefit from atezolizumab.
IMvigor010 的中期结果显示，与观察相比，接受辅助阿替利珠单抗（抗 PD-L1）治疗的循环肿瘤 DNA（ctDNA）阳性肌肉浸润性膀胱癌（MIUC）患者的总生存期（OS）有获益。
按 ctDNA 状态报告更新的 OS 和安全性数据。
设计、地点和参与者：这是一项来自全球、开放标签、随机、3 期试验（NCT02450331）的分析，纳入了可评估第 1 周期第 1 天（C1D1）ctDNA 样本的意向治疗（ITT）人群。
阿替利珠单抗（1200 mg，每 3 周 1 次）或观察 ≤1 年。
评估了 ctDNA 状态下的 OS、复发率和安全性。
在纳入的 809 例 ITT 患者中的 581 例（37%）中，214 例（37%）ctDNA 阳性。与观察相比，阿替利珠单抗并未改善 ITT 患者的 OS（风险比[HR]0.91 [95%置信区间 {CI}0.73-1.13]；中位随访 46.8 个月[四分位距，36.1-53.6]）。在观察组中，ctDNA 阳性与阴性与较短的 OS 相关（HR 6.3 [95% CI 4.3-9.3]）。ctDNA 阳性识别出阿替利珠单抗与观察相比 OS 获益的患者（HR 0.59 [95% CI 0.42-0.83]）。与阿替利珠单抗相比，ctDNA 水平的更大降低（C3D1）与更长的 OS 相关（100%清除，60.0 个月[95% CI 35.5-不可估计]；50%-99%降低，34.3 个月[95% CI 15.2-不可估计]；<50%降低，19.9 个月[95% CI 16.4-32.2]）。与单独 C1D1 相比，C1D1 + C3D1 时的 ctDNA 阳性与更高的复发率相关（68% vs 57%）。无论 ctDNA 状态如何，阿替利珠单抗的不良事件发生率均高于观察组。研究的局限性在于其探索性设计。
有证据表明，MIUC 中的 ctDNA 阳性预示着阿替利珠单抗有益。一项正在进行的前瞻性研究将进一步评估这些发现。
在手术后患有膀胱癌的患者中，如果在其血液中检测到肿瘤源性 DNA，则其生存情况较差；与观察相比，这些患者接受阿替利珠单抗治疗的生存时间更长。血液中的肿瘤源性 DNA 可能识别出从阿替利珠单抗治疗中获益的患者。
