Second Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, National & Kapodistrian University of Athens, Athens, Greece.
Department of Urology, University Clinic Schleswig-Holstein-Lu¨beck, Lu¨beck, Germany.
ESMO Open. 2021 Jun;6(3):100152. doi: 10.1016/j.esmoop.2021.100152. Epub 2021 May 10.
The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC.
This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test.
Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes.
Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.
在铂类耐药的晚期尿路上皮癌（aUC）中，预处理因素对免疫检查点抑制的影响值得进一步评估。本研究旨在探讨贝伦蒙特危险因素、末次化疗时间（TFLC）、既往治疗和 PD-L1 表达与铂类耐药的 aUC 患者接受阿特珠单抗疗效的关系。
这是一项回顾性单臂 IIIb 期 SAUL 研究（NCT02928406）中接受过顺铂或卡铂治疗的患者的事后分析。患者接受阿特珠单抗 1200mg，每 3 周静脉注射 1 次。主要终点为总生存期（OS）。采用 Cox 回归和长期秩检验分析关系。
在 SAUL 中 997 例患者中，969 例符合本分析条件。贝伦蒙特危险因素的数量与 OS 相关（P<0.001）；0、1 和 2-3 个危险因素的中位 OS（mOS）分别为 17.9、8.9 和 3.3 个月。OS 与 TFLC（P<0.001）、程序性死亡配体 1（PD-L1）表达（P=0.002）和围手术期化疗（P=0.013）之间也存在显著相关性；TFLC≤6 个月和>6 个月的 mOS 分别为 6.97 和 11.63 个月，肿瘤浸润免疫细胞（IC）<1%的 PD-L1 表达（IC0）/肿瘤浸润 IC 中 1%至<5%的表达（IC1）与肿瘤浸润 IC 中≥5%的表达（IC2/3）分别为 7.75 和 11.6 个月，围手术期化疗和无围手术期化疗的 mOS 分别为 10.2 和 7.8 个月。铂类化合物的类型和既往治疗线数与结局无关。
铂类耐药后阿特珠单抗在 aUC 中具有活性，与既往铂类化合物和治疗线数无关。贝伦蒙特风险分层、PD-L1 表达、TFLC 和围手术期化疗是二线阿特珠单抗治疗 OS 的预后因素，表明需要为接受免疫治疗的 aUC 患者制定新的预后标志物。
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