PMID- 33612455 OWN - NLM STAT- MEDLINE DCOM- 20220201 LR - 20220201 IS - 2588-9311 (Electronic) IS - 2588-9311 (Linking) VI - 4 IP - 3 DP - 2021 Jun TI - Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial. PG - 456-463 LID - S2588-9311(20)30206-6 [pii] LID - 10.1016/j.euo.2020.11.010 [doi] AB - BACKGROUND: There are limited data on toxicity and surgical safety associated with neoadjuvant programmed death ligand 1 (PD-L1) inhibitors prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). OBJECTIVE: To present a comprehensive safety analysis of the largest neoadjuvant series, with focus on timing and severity of toxicity and surgical complications occurring after neoadjuvant atezolizumab in patients with MIBC enrolled in the ABACUS trial. DESIGN, SETTING, AND PARTICIPANTS: ABACUS (NCT02662309) is an open-label, multicenter, phase II trial for patients with histologically confirmed (T2-T4aN0M0) MIBC, awaiting RC. Patients either were ineligible or refused cisplatin-based neoadjuvant chemotherapy. INTERVENTION: Two cycles of neoadjuvant atezolizumab (1200 mg, every 3 wk) followed by RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Description of atezolizumab toxicity profile in the neoadjuvant setting, impact on surgery, and delayed immune-mediated adverse events (AEs) were assessed. RESULTS AND LIMITATIONS: Ninety-five patients received treatment. Of them, 44% (42/95) had atezolizumab-related AEs during the neoadjuvant period (fatigue [20%], decreased appetite [6%], and transaminases increased [6%]). Treatment-related grade 3-5 AEs occurred in 11% (10/95) of patients during the study. Of the patients, 21% (20/95) received only one cycle of atezolizumab due to AEs; 92% (87/95) underwent RC. No surgery was delayed due to atezolizumab-related toxicities. Surgical complications occurred in 62% (54/87) of patients. Of these patients, 43% (37/87) and 20% (17/87) had minor (grade 1-2) and major (grade 3-5) complications, respectively. Thirteen of 87 (15%) patients had post-RC atezolizumab-related AEs, including adrenal insufficiency and transaminases increased. Three deaths occurred during the period of study-related interventions (one non-treatment-related aspiration pneumonia, one immune-related myocardial infarction, and one cardiogenic shock after RC). Not all surgical safety parameters were available. CONCLUSIONS: Two cycles of neoadjuvant atezolizumab are well tolerated and do not seem to impact surgical complication rates. Owing to the long half-life, AEs may occur in the postoperative period, including endocrine abnormalities requiring attention and intervention. PATIENT SUMMARY: Here, we report a comprehensive dataset of patients receiving neoadjuvant immune checkpoint inhibitors before radical cystectomy. Treatment with neoadjuvant atezolizumab is safe and does not seem to complicate surgery significantly. CI - Copyright (c) 2020. Published by Elsevier B.V. FAU - Szabados, Bernadett AU - Szabados B AD - Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. FAU - Rodriguez-Vida, Alejo AU - Rodriguez-Vida A AD - Department of Medical Oncology, Hospital del Mar, Barcelona, Spain. FAU - Duran, Ignacio AU - Duran I AD - Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocio, CSIC and Universidad de Sevilla, Seville, Spain. FAU - Crabb, Simon J AU - Crabb SJ AD - Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK. FAU - Van Der Heijden, Michiel S AU - Van Der Heijden MS AD - Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Pous, Albert Font AU - Pous AF AD - Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B.ARGO)-IGTP, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. FAU - Gravis, Gwenaelle AU - Gravis G AD - Medical Oncology Department, Institut Paoli-Calmettes, Aix-Marseille Universite, Inserm, CNRS, CRCM, Marseille, France. FAU - Herranz, Urbano Anido AU - Herranz UA AD - Department of Medical Oncology, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. FAU - Protheroe, Andrew AU - Protheroe A AD - Maimonides Institute for Biomedical Research oh Cordoba (IMIBIC), Hospital Universitario Reina Sofia, Cordoba, Spain. FAU - Ravaud, Alain AU - Ravaud A AD - Department of Medical Oncology, Hopital Saint-Andre, University of Bordeaux-CHU Bordeaux, Bordeaux, France. FAU - Maillet, Denis AU - Maillet D AD - Department of Medical Oncology, Hospital Lyon Sud, Lyon, France. FAU - Mendez-Vidal, Maria J AU - Mendez-Vidal MJ AD - Department of Medical Oncology, Reina Sofia University Hospital, Cordoba, Spain. FAU - Suarez, Cristina AU - Suarez C AD - Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Linch, Mark AU - Linch M AD - Department of Oncology, University College London Cancer Institute, London, UK. FAU - Prendergast, Aaron AU - Prendergast A AD - Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. FAU - Tyson, Charlotte AU - Tyson C AD - Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. FAU - Mousa, Kelly AU - Mousa K AD - Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. FAU - Castellano, Daniel AU - Castellano D AD - Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain. FAU - Powles, Thomas AU - Powles T AD - Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: t.powles@qmul.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT02662309 GR - CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210218 PL - Netherlands TA - Eur Urol Oncol JT - European urology oncology JID - 101724904 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 52CMI0WC3Y (atezolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Cystectomy/adverse effects MH - Humans MH - Muscles MH - *Neoadjuvant Therapy/adverse effects MH - *Urinary Bladder Neoplasms/drug therapy/surgery OTO - NOTNLM OT - Atezolizumab OT - Muscle-invasive bladder cancer OT - Programmed death ligand 1 OT - Safety OT - Surgical complications OT - Toxicity EDAT- 2021/02/23 06:00 MHDA- 2022/02/02 06:00 CRDT- 2021/02/22 05:49 PHST- 2020/09/09 00:00 [received] PHST- 2020/11/02 00:00 [revised] PHST- 2020/11/30 00:00 [accepted] PHST- 2021/02/23 06:00 [pubmed] PHST- 2022/02/02 06:00 [medline] PHST- 2021/02/22 05:49 [entrez] AID - S2588-9311(20)30206-6 [pii] AID - 10.1016/j.euo.2020.11.010 [doi] PST - ppublish SO - Eur Urol Oncol. 2021 Jun;4(3):456-463. doi: 10.1016/j.euo.2020.11.010. Epub 2021 Feb 18.