SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy

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A. Bamias¹  A.S. Merseburger²  Y. Loriot³  N. James⁴  E. Choy⁵  D. Castellano⁶  F. Lopez-Rios⁷  F. Calabrò⁸  M. Kramer²  G. de Velasco⁶  R. Zakopoulou⁹  K. Tzannis¹  C.N. Sternberg^1,10 

[1]Second Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, National & Kapodistrian University of Athens

[2]Department of Urology, University Clinic Schleswig-Holstein-Lu¨beck

[3]Department of Cancer Medicine, Institut Gustave Roussy

[4]Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust

[5]CREATE Centre, Division of Infection and Immunity, Cardiff University

[6]Medical Oncology, Hospital Universitario 12 de Octubre

[7]Pathology Laboratory of Therapeutic Targets, HM Sanchinarro University Hospital

[8]GU Oncology Unit, San Camillo and Forlanini Hospital

[9]Clinical Therapeutics, University of Athens

[10]Englander Institute for Precision Medicine, Department of Medical Oncology, Weill Cornell Medicine, Meyer Cancer Center

关键词: bladder cancer;    immunotherapy;    PD-L1;    platinum;    prognostic factors;    urothelial carcinoma;   

DOI  :  10.1016/j.esmoop.2021.100152

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background 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.Patients and methods 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.Results 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 (P6 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.Conclusions 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.

【 授权许可】

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