Bernadett Szabados1, Alejo Rodriguez-Vida2, Ignacio Durán3, Simon J Crabb4, Michiel S Van Der Heijden5, Albert Font Pous6, Gwenaelle Gravis7, Urbano Anido Herranz8, Andrew Protheroe9, Alain Ravaud10, Denis Maillet11, Maria J Mendez-Vidal12, Cristina Suárez13, Mark Linch14, Aaron Prendergast1, Charlotte Tyson1, Kelly Mousa1, Daniel Castellano15, Thomas Powles16. 1. Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. 2. Department of Medical Oncology, Hospital del Mar, Barcelona, Spain. 3. Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocio, CSIC and Universidad de Sevilla, Seville, Spain. 4. Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK. 5. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B.ARGO)-IGTP, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 7. Medical Oncology Department, Institut Paoli-Calmettes, Aix-Marseille Université, Inserm, CNRS, CRCM, Marseille, France. 8. Department of Medical Oncology, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. 9. Maimonides Institute for Biomedical Research oh Cordoba (IMIBIC), Hospital Universitario Reina Sofia, Cordoba, Spain. 10. Department of Medical Oncology, Hopital Saint-Andre, University of Bordeaux-CHU Bordeaux, Bordeaux, France. 11. Department of Medical Oncology, Hospital Lyon Sud, Lyon, France. 12. Department of Medical Oncology, Reina Sofia University Hospital, Cordoba, Spain. 13. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. 14. Department of Oncology, University College London Cancer Institute, London, UK. 15. Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain. 16. Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: t.powles@qmul.ac.uk.
Abstract
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.
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.
Authors: Maria Lucia Iacovino; Chiara Carmen Miceli; Marco De Felice; Biagio Barone; Luca Pompella; Francesco Chiancone; Erika Di Zazzo; Giuseppe Tirino; Carminia Maria Della Corte; Ciro Imbimbo; Ferdinando De Vita; Felice Crocetto Journal: Int J Mol Sci Date: 2022-01-20 Impact factor: 5.923