Atezolizumab for locally advanced/metastatic urothelial carcinoma within the compassionate use program in Spain: The IMcompass study.
Authors: Climent Duran Miguel Angel A. , Perez-Gracia Jose Luis , Arranz Arija Jose Angel , Alvarez-Fernandez Carlos , Gomez Mediavilla Jenifer , Rodriguez Angel , Vazquez-Estevez Sergio , Jurado Jose Miguel , Santander Carmen , Bonfill Teresa , Molins Palau Carmen , Perez Ramirez Sara , Pimentel Cáceres Paola , Arnáiz Pablo , Garate Zita , Soto Atenea , Puente Javier 
Published: February 2022

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Background: Atezolizumab is a monoclonal antibody with proven efficacy in clinical trials for advanced or metastatic urothelial carcinoma (UC) after progression to platinum-based chemotherapy. Following EMA marketing authorization and before prizing and reimbursement was granted in Spain, the Spanish Medicines Agency authorized a compassionate use program. We describe the patient characteristics and atezolizumab effectiveness in this compassionate use program. Methods: It was a multicentre cohort study based on the retrospective chart review of patients with inoperable locally advanced or metastatic UC who received atezolizumab, following progression to platinum-based chemotherapy, under the compassionate use program in Spain. The primary endpoint was their demographic and clinical characterization. Secondary endpoints included the best response to atezolizumab, progression-free survival (PFS) and overall survival (OS). Results: 109 evaluable patients were included, with a median age (interquartile range, IQR) of 68.0 years (62.0-75.0), 87 males (79.8%) and 96 Caucasians (88.1%). Median age (IQR) at diagnosis was 64.0 years (58.0-72.0) and 92 (84.4%) had pure urothelial carcinoma. Twenty-four (22.0%) had received BCG, 18 (16.5%) neoadjuvant treatment, 19 (17.4%) adjuvant treatment, and 19 (17.4%) radiotherapy for primary tumour. Regarding prior metastatic treatments, 98 (89.9%) had received first-line chemotherapy, 46 (42.2%) second line, 19 (17.4%) third line, and 5 (4.6%) more lines. When starting atezolizumab, median age (IQR) was 69.0 years (62.0-74.0) and 105 (96.3%) had metastases: 71 (65.1%) in lymph nodes and 64 (58.7%) visceral (skeletal n = 31, lung n = 29, liver n = 26, other n = 13). Atezolizumab was used for a median (IQR) of 2.8 (1.4-8.4) months and 5.0 (3.0-13.0) administered doses. The overall response rate was 23.8%, with 6 patients (5.5%) achieving complete response and 20 (18.3%) partial response. Stable disease was observed in 21 (19.3%), progression in 44 (40.4%) and response was not evaluable in 18 (16.5%). The median PFS (95% CI) was 3.7 months (2.8-5.8), with PFS rates at months 3, 6, 9 and 12 of 57.5%, 38.0%, 30.5% and 26.1%, respectively. The median OS (95% CI) reached 8.5 (6.6-12.6) months, with a 12-month OS of 43.4%. Twenty-three patients (21.1%) reported 26 delays (adverse event n = 16, intercurrent event n = 10) and 2 (1.8%) interruptions (adverse event n = 1, intercurrent event n = 1). Atezolizumab was discontinued in 64 (58.7%) due to disease progression (n = 43, 67.2%), death (n = 13, 20.3%), adverse events (n = 7, 10.9%) and lost to follow-up (n = 1, 1.6%). Conclusions: This study provides real-world evidence on the characteristics of patients with advanced or metastatic UC treated with atezolizumab under the Spanish compassionate use program, supporting its effectiveness in the clinical setting.